Rate Of Lactic Acid Production Research Articles

Effects of Freezing Raw Yak Milk on the Fermentation Performance and Storage Quality of Yogurt.

In this study, the effects of freezing yak milk at -20 °C and -40 °C for 30, 90 and 180 days on the fermentation characteristics and storage quality of the corresponding yogurt were discussed. The results showed that, compared with that of yogurt made from fresh yak milk, the lactic acid bacteria (LAB) growth and acid production rate of the yogurt in the -20 °C group decreased at 90 d. The water-holding capacity, viscosity and hardness decreased during storage, and a sour taste was prominent, while no significant changes were observed in the -40 °C group. At 180 d of freezing, the post-acidification of the yogurt in the -20 °C and -40 °C groups increased after 21 d of storage. Compared with the -40 °C group, the -20 °C group showed a significant decrease in LAB counts, a decrease in pH value to 3.63-3.80 and poor texture and sensory quality.

Valorization of orange peels exploiting fungal solid-state and lacto-fermentation.

Orange peels can serve as a cost-effective raw material for the production of lactic acid. Indeed, given their high concentration of carbohydrates and low content of lignin, they represent an important source of fermentable sugars, recoverable after a hydrolytic step. In the present article, the fermented solid, obtained after 5 days of Aspergillus awamori growth, was used as the only source of enzymes, mainly composed of xylanase (40.6IU g-1 of dried washed orange peels) and exo-polygalacturonase (16.3IU g-1 of dried washed orange peels) activities. After the hydrolysis, the highest concentration of reducing sugars (24.4g L-1 ) was achieved with 20% fermented and 80% non-fermented orange peels. The hydrolysate was fermented with three lactic acid bacteria strains (Lacticaseibacillus casei 2246 and 2240 and Lacticaseibacillus rhamnosus 1019) which demonstrated good growth ability. The yeast extract supplementation increased the lactic acid production rate and yield. Overall, L. casei 2246 produced the highest concentration of lactic acid in mono-culture. To the best of our knowledge this is the first study exploiting orange peels as low-cost raw material for the production of lactic acid avoiding the employment of commercial enzymes. The enzymes necessary for the hydrolyses were directly produced during A. awamori fermentation and the reducing sugars obtained were fermented for lactic acid production. Despite this preliminary work carried out to study the feasibility of this approach, the concentrations of reducing sugars and lactic acid produced were encouraging, leaving open the possibility of other studies for the optimization of the strategy proposed here. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Effects of sodium diacetate and microbial inoculants on fermentation of forage rye

Rye (Secale cereale L.) is a valuable annual forage crop in Korea but there is limited information about the impact of chemical and biological additives on fermentation characteristics of the crop. This experiment was conducted to investigate fermentation dynamics of wilted forage rye treated with the following six additives; control (no additive), sodium diacetate applied at 3 g/kg wilted forage weight (SDA3), 6 g/kg wilted forage weight (SDA6), inoculations (106 CFU/g wilted forage) of Lactobacillus plantarum (LP), L. buchneri (LB), or LP+LB. The ensiled rye sampled at 1, 2, 3, 5, 10, 20, 30, and 45 days indicated that the acidification occurred fast within five days of storage than the rest of the storage period. The microbial inoculants decline the pH of ensiled forage, more rapidly than the control or SDA treated, which accompanied by the decrease of water-soluble carbohydrates and increase of lactic acid. Compared with the control silage, all treatments suppressed ammonia-nitrogen formation below to 35 g/kg DM throughout the sampling period. Suppression of total microbial counting occurred in SDA6, LP, and LP + LB. The lactic acid production rates were generally higher in microbial inoculation treatments. Acetic acid concentration was lowest in the LP-treated silage and highest in the SDA- and LB-treated silages. The in vitro dry matter (DM) digestibility and total digestible nutrients were the highest in the silage treated with SDA (6 g/kg) at day 45 of ensiling. Based on lower ammonia-nitrogen concentrations and higher feed value, ensiling forage rye treated with SDA at 6 g/kg is promising through enhanced silage quality.

Co-expression of Xylose Transporter and Fructose-Bisphosphate Aldolase Enhances the Utilization of Xylose by Lactococcus lactis IO-1.

The raw material cost of lactic acid fermentation accounts for the main part of the production cost, and this necessitates the exploration of the efficient use of cheap raw materials in lactic acid production. We compared the outcomes of the homologous expressions of xylose transporters (xylFGH, xylE, araE, and xylT), 6-phosphofructokinase (pfkA), fructose-bisphosphate aldolase (fbaA), and their co-expression in Lactococcus lactis IO-1 on lactic acid production using xylose as the raw material. We found that the production rate of lactic acid on xylose fermentation by L. lactis IO-1 overexpressing fbaA was the highest (14.42%). Among the xylose transporters investigated, XylT had the strongest xylose transport capacity in L. lactis IO-1, with an increase in the lactic acid production rate by 10.38%. The genes near the overexpression of fbaA or xylT in the metabolic pathway were more upregulated than the distant genes. The co-expression of fbaA and xylT increased the production rate of lactic acid by 27.84% on xylose fermentation by L. lactis IO-1. This work presents a novel strategy for the simultaneous enhancement of the expression of important genes at the beginning and midway of the xylose metabolic pathway of L. lactis IO-1, which could greatly improve the target production.

Solvent-free synthesis of a zirconium-carbon coordination catalyst for efficient aqueous-phase production of lactic acid from xylose

It is highly desirable but of challenge to develop an efficient process for lactic acid (LaA) production from xylose performed in water. Herein, a novel catalyst prepared via a facile solvent-free coordination route is developed to efficiently produce LaA from xylose in water. The structural properties of the prepared catalyst and the reaction conditions are systematically investigated. The production rate of LaA at 190 °C in water is up to 1.8 h−1, outperforming the most recent reports (below 1.1 h−1). Detailed experimental and characteristic studies reveal that the presence of Lewis acidic sites and basic sites in the catalyst structure can not only lower the energy barrier of xylose conversion but also boost the efficient conversion of the active reaction intermediates into LaA. The findings of this work will provide a new approach for the efficient production of LaA from carbohydrates.

Lactic acid fermentation of food waste at acidic conditions in a semicontinuous system: effect of HRT and OLR changes

Lactic acid production through fermentation is an established technology, however, improvements are necessary to reduce the process costs and to decrease its market price. Lactic acid is used in many industrial sectors and its market has increased in the last decade for its use as the raw material for polylactic acid product. Using food waste as a cheap and renewable substrate, as well as fermentation at uncontrolled pH, helps to make the production cheaper and to simplify the downstream purification process. Lactic acid production at acidic conditions and the role of varying organic loading rate (OLR) and hydraulic retention time (HRT) were tested in two different semicontinuous batch fermentation systems. Reactor performances indicated that lactic acid fermentation was still possible at pH < 3.5 and even up to a pH of 2.95. The highest lactic acid production was recorded at 14-day HRT, 2.14 g VS/L·day OLR, and pH 3.11 with a maximum lactic acid concentration of 8.72 g/L and a relative yield of 0.82 g lactate/g carbohydrates. The fermentation microbial community was dominated by Lactobacillus strains, the organism mainly responsible for lactic acid conversion from carbohydrates. This study shows that low pH fermentation is a key parameter to improve lactic acid production from food waste in a semicontinuous system. Acidic pH favored both the selection of Lactobacillus strains and inhibited VFA producers from utilizing lactic acid as primary substrate, thus promoting the accumulation of lactic acid. Finally, production yields tend to decrease with high OLR and low HRT, while lactic acid production rates showed the opposite trend.

An Assessment of the Lactic Acid-Producing Potential of Bacterial Strains Isolated from Food Waste

Lactic acid (LA) is widely used in many industries as a crucial starting material in food products, bio-based materials, and biodegradable polymers. The goals of this research were to isolate LA bacteria from food wastes, assess their potential for LA production, and study their growth characteristics. In this study, six bacterial strains were isolated from food waste and identified using 16S rRNA gene sequencing; namely, Weissella viridescens WJ39, Leuconostoc lactis YS33, Leuconostoc citreum KD42, Leuconostoc mesenteroides VN60, Macrococcus caseolyticus FCI29, and Weissella confusa RG41. W. viridescens WJ39 showed the highest potential for lactic acid production (17.56 g L−1day−1), and the lowest potential was found in L. lactis YS33 (14.09 g L−1day−1). There were significant differences (p &lt; 0.05) in the LA production rates among Weissella spp., Leuconostoc spp., and Macrococcus spp. Moreover, dramatic differences in growth rate were observed among the six strains. W. viridescens WJ39 exhibited the highest growth rate (0.80 h−1), while M. caseolyticus FCI29 exhibited the lowest growth rate (0.57 h−1). W. viridescens WJ39 also exhibited lactic acid production (at a rate around 2 g L−1day−1) in a lab incubation experiment with food waste as a nutrient source. The draft genome of W. viridescens WJ39 with 16 contigs was constructed with an N50 of 215217 bp. The genome size was approximately 1.54 Mb, with a GC content of 41%. A hicD gene, known to catalyze the conversion of pyruvate to D-lactate, was discovered in the genome. This study illustrated the potential for the production of lactic acid from food waste with lactic acid bacteria.

High-rate conversion of lactic acid-rich streams to caproic acid in a fermentative granular system

Lactic acid-driven chain elongation enables upgrading low-value organic streams into caproic acid. Recently, volumetric production rates over 0.5 g L-1 h-1have been reported for carbohydrate-rich streams in expanded granular sludge bed (EGSB) reactors. However, many target streams contain mixtures of carbohydrates and lactic acid, and little is known about their impact on product profile and microbial ecology, or the importance of carbohydrates as substrate to achieve high rates. This manuscript investigated varying glucose-to-lactate ratios and observed that decreasing glucose-content eliminated odd-chain by-products, while glucose omission required acetic acid addition to support lactic acid conversion. Decreasing the glucose-content fed resulted in decreasing amounts of granular biomass, with the disappearance of granules when no glucose was fed. Lowering the HRT to 0.3 days while feeding only lactic and acetic acid likely triggered re-granulation, enabling the highest lactic acid-driven caproic acid production rates reported thus far at 16.4 ± 1.7 g L-1 d-1.

Direct conversion of cellulose to l-lactic acid by a novel thermophilic Caldicellulosiruptor strain

BackgroundConsolidated bioprocessing (CBP) of lignocellulosic biomass to l-lactic acid using thermophilic cellulolytic/hemicellulolytic bacteria provides a promising solution for efficient lignocellulose conversion without the need for additional cellulolytic/hemicellulolytic enzymes. Most studies on the mesophilic and thermophilic CBP of lignocellulose to lactic acid concentrate on cultivation of non-cellulolytic mesophilic and thermophilic bacteria at temperatures of 30–55 °C with external addition of cellulases/hemicellulases for saccharification of substrates.Resultsl-Lactic acid was generated by fermenting microcrystalline cellulose or lignocellulosic substrates with a novel thermophilic anaerobic bacterium Caldicellulosiruptor sp. DIB 104C without adding externally produced cellulolytic/hemicellulolytic enzymes. Selection of this novel bacterium strain for lactic acid production is described as well as the adaptive evolution towards increasing the l-lactic acid concentration from 6 to 70 g/l on microcrystalline cellulose. The evolved strains grown on microcrystalline cellulose show a maximum lactic acid production rate of 1.0 g/l*h and a lactic acid ratio in the total organic fermentation products of 96 wt%. The enantiomeric purity of the l-lactic acid generated is 99.4%. In addition, the lactic acid production by these strains on several other types of cellulose and lignocellulosic feedstocks is also reported.ConclusionsThe evolved strains originating from Caldicellulosiruptor sp. DIB 104C were capable of producing unexpectedly large amounts of l-lactic acid from microcrystalline cellulose in fermenters. These strains produce l-lactic acid also from lignocellulosic feedstocks and thus represent an ideal starting point for development of a highly integrated commercial l-lactic acid production process from such feedstocks.

A New Approach to Bicarbonate Addition During Hemodialysis: Testing Model Predictions in a Patient Cohort

In this study, we present a new protocol for kidney replacement therapy (hemodialysis), based on an explicitly solvable mathematical model. With current protocols, the high and constant level of bath bicarbonate (HCO₃^&#x2212;) used to prevent metabolic acidosis leads to very rapid delivery of HCO₃^&#x2212; into the patient during the first part of the therapy. This rapid alkalinization elicits a robust buffer response that, paradoxically, consumes more HCO₃^&#x2212; than is added during the remainder of the treatment. In previous studies, we developed an analytical model that allows one to quantify these events and tested alternative protocols manipulating the rate of rise in blood bicarbonate concentration (HCO₃^&#x2212;). The protocol tested in this paper enforces a more gradual increase in blood HCO₃^&#x2212;, by means of a model-based staircase adjustment of bath HCO₃^&#x2212;. Model equations predict a reduction of buffer response and rate of organic acid production. These predictions are tested in 20 stable outpatients receiving hemodialysis. We find that the proposed protocol achieves the desired profile of blood HCO₃^&#x2212; with good accuracy and reduces the total buffer response by 1/3 and the rate of lactic acid production by at least 1/4, as compared to conventional therapy. Although more studies are needed, we believe that our work will pave the way for a more rational approach to correction of acidosis during hemodialysis. Article Highlights <list list-type="bullet"><list-item><label>&#x2022;</label> Our study tests an analytic model designed to enforce a more gradual rate of bicarbonate delivery during hemodialysis. </list-item><list-item><label>&#x2022;</label> Using our model, we show that we can reduce the excessive buffer response and lactic acid production that occur with the conventional approach. </list-item><list-item><label>&#x2022;</label> We demonstrate that our model can provide a rational approach to bicarbonate addition during treatment. </list-item> </list>

Microbial Interactions between Amylolytic and Non-Amylolytic Lactic Acid Bacteria Strains Isolated during the Fermentation of Pozol.

Pozol is a Mexican beverage prepared from fermented nixtamalized maize dough. To contribute to understanding its complex microbial ecology, the effect of inoculating on MRS-starch pure and mixed cultures of amylolytic Sii-25124 and non-amylolytic W. confusa 17, isolated from pozol, were studied on their interactions and fermentation parameters. These were compared with L. plantarum A6, an amylolytic strain isolated from cassava. Microbial growth, kinetic parameters, amylolytic activity, lactic acid production, and hydrolysis products from starch fermentation were measured. The population dynamics were followed by qPCR. L. plantarum A6 showed higher enzymatic activity, lactic acid, biomass production, and kinetic parameters than pozol LAB in pure cultures. Mixed culture of each pozol LAB with L. plantarum A6 showed a significant decrease in amylolytic activity, lactic acid yield, specific growth rate, and specific rate of amylase production. The interaction between Sii-25124 and W. confusa 17 increased the global maximum specific growth rate (µ), the lactic acid yield from starch (Ylac/s), lactic acid yield from biomass (Ylac/x), and specific rate of lactic acid production (qlac) by 15, 30, 30, and 40%, respectively, compared with the pure culture of Sii-25124. Interactions between the two strains are essential for this fermentation.

Ultrasonication-assisted kefir production and its effect on fermentation time and EPS production

In this study, microbial activity enhancement effects of ultrasonic sound waves in kefir fermentation were investigated. For this purpose, the effect of ultrasonication (5 min continuous, 22 mm prob, 24 kHz, 400 W, 30% amplitude) on fermentation time was evaluated in kefir production. The microbiological analysis, pH measurement, titratable acidity (lactic acid %) were performed during the fermentation. The produced EPS was measured at the end of the fermentation. The fermentation time was decreased 1 h by ultrasonication applied in kefir fermentation. Even more, the ultrasonication treatment was improved EPS and lactic acid production rate. However, it did not affect production of EPS and lactic acid in kefir statistically (p > 0.05).

Mathematical Modeling of Lactobacillus paracasei CBA L74 Growth during Rice Flour Fermentation Performed with and without pH Control

The mathematical modeling of fermentation processes allows for the formulation of predictions about the kinetics of biomass growth and metabolite production as well as setting or verifying the best operative conditions in view of the economical convenience of the process. For this purpose, we performed a kinetic study of a rice flour fermentation process using Lactobacillus paracasei CBA L74 with and without pH control; the pH value was set to 5.8 under pH control. Monod, Logistic, and Contois models were proposed to describe the bacterial growth rate in both conditions. The best mathematical model, which was able to describe the experimental data obtained without pH control, was the Contois model, as the specific growth rate was influenced by both the glucose reduction (from 14.31 g/L to 10.22 g/L) and the biomass production (2 log growth) that occurred during fermentation. Conversely, when pH control was implemented, both Monod and Contois models satisfactorily described the specific growth rate trend. The estimated kinetic parameters confirmed that biomass production (2 log growth) and glucose consumption (from 14.31 g/L to 6.06 g/L) did not affect the microorganism’s growth capacity when the fermenting medium was maintained at an optimal pH. The lactic acid production rate described by the Luedeking–Piret model did not appear to be linked to growth in the absence of pH control while, on the other hand, this model was unsuitable for describing the experimental lactic acid concentration when pH control was applied. The kinetic modeling of lactic acid production and the percentage of added glucose in the protocol with controlled pH will be optimized in the future.

Effect of initial pH and substrate concentration on the lactic acid production from cassava wastewater fermentation by an enriched culture of acidogenic microorganisms.

Recently, cassava processing wastewater has been considered an alternative substrate for lactic acid production due to its appreciable carbohydrate levels. The authors carried out different batch reactor trials aiming to favor the production of lactic acid through the fermentation of non-sterilized cassava wastewater by an enriched culture of acidogenic microorganisms. To this end, the impact of different initial pHs (4.5, 5.0, 5.7, 6.5, and 7.0) and different initial substrate concentrations (10, 15.8, 30, 44.2, and 50g/L) in terms of glucose on lactic acid production yield (Y) was evaluated by applying the design of experiment (DoE) known as central composite rotatable design (CCRD). The highest rate of lactic acid production (40g/L) occurred with an initial pH of 6.5 and an initial substrate concentration of 50g/L. The maximum yield was higher in trials T1, T2, T4, T5, and T8, reaching values of 0.80, 0.62, 0.60, 0.96, and 0.70g/g, respectively. The maximum lactic acid productivity (P), of 0.60 and 0.73gL-1 hr-1 , was observed in trials T5 and T8, respectively. The enriched culture of acidogenic microorganisms was shown to favor the production of lactic acid, since the production of other acids, such as acetic and propionic acid, did not exceed 3.5 and 4.5g/L, respectively. © 2020 Water Environment Federation PRACTITIONER POINTS: Cassava wastewater presented potential to lactic acid production. The CCRD showed that highest lactic acid concentrations (40g/L). The adoption of cassava wastewater or manipueira as a substrate resulted in important information on the tendency to obtain value-added products such as lactic acid.

Requirement of de novo synthesis of pyruvate carboxylase in long-term succinic acid production in Corynebacterium glutamicum.

Protein turnover through de novo synthesis is critical for sustainable cellular functions. We previously found that glucose consumption rate in Corynebacterium glutamicum under anaerobic conditions increased at temperature higher than the upper limit of growth temperature. Here, we showed that production of lactic and succinic acids increased at higher temperature for long-term (48h) anaerobic reaction in metabolically engineered strains. At 42°C, beyond the upper limit of growth temperature range, biomass-specific lactic acid production rate was 8% higher than that at 30°C, the optimal growth temperature. In contrast, biomass-specific succinic acid production rate was highest at 36°C, 28% higher than that at 30°C, although the production at 42°C was still 23% higher than that at 30°C. As enzymes are usually unstable at high temperatures, we investigated whether protein turnover of metabolic enzymes is required for the production of lactic and succinic acids under these conditions. Interestingly, when de novo protein synthesis was inhibited by addition of chloramphenicol, after 6h, only succinic acid production was inhibited. Because glycolytic enzymes are involved in both lactic and succinic acids synthesis, enzymes in the anaplerotic pathway and the tricarboxylic acid (TCA) cycle leading to succinic acid synthesis were likely to be responsible for its decreased production. Among the five enzymes examined, the specific activity of only pyruvate carboxylase was drastically decreased after 48h at 42°C. Thus, the de novo synthesis of pyruvate carboxylase is required for long-term production of succinic acid. Graphical abstract KEY POINTS: • Long-term reaction for organic acids can be improved at temperature beyond ideal growth conditions. • De novo synthesis of pyruvate carboxylase is required for long-term succinic acid production.

Bioreactor Scale-Up and Kinetic Modeling of Lactic Acid and Biomass Production by Enterococcus faecalis SLT13 during Batch Culture on Hydrolyzed Cheese Whey

Kinetic modeling of biomass and lactic acid production by Enterococcus faecalis SLT13 have been developed during batch culture in M17 and Hydrolyzed Cheese Whey (HCW) in 2 L and 20 L bioreactors. The specific growth rate μmax was higher in 20 L bioreactor (1.09 h−1); however, the maximum specific lactic acid production rate qpmax and maximum specific sugar utilization rate qsmax were higher in 2 L bioreactor. Biomass and sugar utilization were affected by lactic acid inhibition in HCW. No effects of substrate inhibition have been observed. Substrate limitation of biomass has been observed on HCW in 20 L bioreactor; the substrate limitation constant for biomass Ksx was 4.229 g/L. Substrate limitation of sugar consumption has been observed on M17 in 2 L bioreactor; the substrate limitation constant for sugar consumption Kss was 2.73 g/L. Compared to experimental data, the model provided good predictions for biomass, sugar consumption, and lactic acid production.

Production of lactic acid by Enterococcus faecalis on waste glycerol from biodiesel production

Waste glycerol from biodiesel production is a valuable raw material that has been used to produce valuable microbial metabolites. In this work, the possibility of microbial utilization of waste glycerol obtained as a by-product in biodiesel production from sunflower and rapeseed oil by the lactic acid bacterium Enterococcus faecalis MK3-10A on a laboratory level was studied. For comparison, pure glycerol and glucose were used as carbon sources. The kinetics of the microbial biomass growth, the carbon source utilization, and the lactic acid production were monitored. The bacterium E. faecalis MK3-10A better grew in the media with glucose or pure glycerol as a carbon source, but the lactic acid production rate was the highest (14.6 mg/(ml/day)) in the medium with waste glycerol from the sunflower oil-based biodiesel production. Therefore, this waste glycerol might be a promising carbon source for lactic acidbacteria cultivation and lactic acid production.

Effects of Some Growth Promoting Substances on the Rate of Growth and Lactic Acid Production by Bifidobacterium bifidum in Sterilized Skim Milk

Effect of some growth promoting substances, i.e., yeast extract, fructose, and peptone on the growth rate and acid production by Bifidobacterium bifidum in sterilized skim milk at 40°C was studied. Growth promoting substances were added to milk in three different concentrations, i.e., 0.1, 0.3, and 0.5%. The obtained results indicated that the three substances resulted in an increased of growth and lactic acid production by Bifidobacterium bifidum. The maximum cell population in the presence of yeast extract reached were 25x104, 12x105 and 21x105 CFU/ml after 12 hours. In the presence of 0.1, 0.3 and 0.5%, respectively

Development of a milk-based medium for the selection of urease-defective mutants of Streptococcus thermophilus

Streptococcus thermophilus strains are used in fermented dairy products for their capacity to metabolize lactose into lactic acid. The rate of lactic acid production in milk is of major economic importance, as rapid acidification prevents growth of undesirable microorganisms. It is also of paramount significance for aroma, texture and flavor of the end product. Besides achieving customer satisfaction, improvement of production rate and operational costs incite industrials into selecting fast acidifying strains. Another important trait of S. thermophilus influencing acidification is the urease, which catabolizes urea into ammonia and has a detrimental effect on acidification. Unfortunately, most of the S. thermophilus strains possess the urease, and the urease-negative ones are necessary for industrial applications. Urease activity is a widely distributed activity in S. thermophilus species, and urease-negative strains are rare. The later are however interesting from an industrial point of view, as they may give faster acidification in dairy applications, because lactic acid is not buffered by urea-derived ammonia. Nowadays, the efforts to improve the characteristics of strains for industrial applications are based on natural strategies such as random mutagenesis. This implies the need of a screening method that is efficient in terms of time and success. In this context, the aim of this study was the development of a new medium that allows selection of urease-defective mutants based on S. thermophilus colony morphology. Discrimination capacity of the new medium was verified using previously characterized urease-negative recombinant strains. The new milk-based medium, applied to industrial S. thermophilus strains subjected to UV mutagenesis, allowed the selection of 3 mutants, partially or completely defective in urease activity. Genetic characterization of urease-defective mutants highlighted the presence of nonsense or missense mutations in the ureA, ureC and ureG genes, thus supporting their phenotype. Evaluation of milk acidification revealed increased performance for one out of three urease-defective mutants compared to wild-type strains.

Statin‐dependent modulation of mitochondrial metabolism in cancer cells is independent of cholesterol content

Statins, widely used to treat hypercholesterolemia, inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme of de novo cholesterol (Chol) synthesis. Statins have been also reported to slow tumor progression. In cancer cells, ATP is generated both by glycolysis and oxidative phosphorylation. Mitochondrial membrane potential (ΔΨ), a readout of mitochondrial metabolism, is sustained by the oxidation of respiratory substrates in the Krebs cycle to generate NADH and flavin adenine dinucleotide, which are further oxidized by the respiratory chain. Here, we studied the short-term effects of statins (3-24 h) on mitochondrial metabolism on cancer cells. Lovastatin (LOV) and simvastatin (SIM) increased ΔΨ in HepG2 and Huh7 human hepatocarcinoma cells and HCC4006 human lung adenocarcinoma cells. Mitochondrial hyperpolarization after LOV and SIM was dose and time dependent. Maximal increase in ΔΨ occurred at 10 µM and 24 h for both statins. The structurally unrelated atorvastatin also hyperpolarized mitochondria in HepG2 cells. Cellular and mitochondrial Chol remained unchanged after SIM. Both LOV and SIM decreased basal respiration, ATP-linked respiration, and ATP production. LOV and SIM did not change the rate of lactic acid production. In summary, statins modulate mitochondrial metabolism in cancer cells independently of the Chol content in cellular membranes without affecting glycolysis.-Christie, C. F., Fang, D., Hunt, E. G., Morris, M. E., Rovini, A., Heslop, K. A., Beeson, G. C., Beeson, C. C., Maldonado, E. N. Statin-dependent modulation of mitochondrial metabolism in cancer cells is independent of cholesterol content.