Mitochondrial Respiratory Enzyme Activities Research Articles

A53. IGF-1 protects myocytes from hypoxia-reoxygenation injury by rescuing mitochondria function

Background: IGF-1 is protective on myocardial ischemia-reperfusion injury but the mechanisms responsible for its salutary effect remain obscured. Methods: This study was conducted in isolated adult rat cardiac myocytes. After 4 hours' pre-culture, myocytes were incubated in the absence or presence of IGF-1 (100 nM) for 60 min and subjected to 60 min hypoxia followed by 30 min reoxygenation at 37 °C. Mitochondrial respiratory enzyme activities and membrane potential (ΔΨm) were determined to evaluate mitochondrial function.

Automated Spectrophotometric Analysis of Mitochondrial Respiratory Chain Complex Enzyme Activities in Cultured Skin Fibroblasts

Mitochondrial respiratory chain complex (RCC) disorders may occur as commonly as 1 in 8500 individuals. Because of the great variability of phenotypic presentations, measurement of individual RCC enzyme activities is a crucial diagnostic process. Current assay methods are time-consuming and labor-intensive and thus constitute a major impediment to clinical practice. A method with a faster turnaround time would therefore be beneficial. We developed an automated spectrophotometric method for measuring the respiratory chain enzyme activities of complex I, complex II + III, and complex IV with the Hitachi 912, an automated spectrophotometer. Mitochondrial citrate synthase was also determined for normalization of the RCC activities. A blinded method comparison with samples from an external testing center yielded a 91% concordance of interpretations. Mean intraassay imprecision (as CV; n = 20) in a single batch analysis of each RCC was 5.9%. Interassay imprecision, evaluated on 2 samples harvested and analyzed 3 times each, gave mean CVs of 10%-18%. With this automated method, a panel of RCC enzyme activities can be determined in <2 h. In addition, an immunoblot assay using monoclonal antibodies against specific subunits of RCC enzyme complexes can be informative in cases of borderline enzyme activity. Our results suggest that in vitro diagnosis of RCC enzyme deficiencies in skin fibroblasts is an effective alternative to invasive muscle biopsy.

Effects of Shark Hepatic Stimulator Substance on the Function and Antioxidant Capacity of Liver Mitochondria in an Animal Model of Acute Liver Injury

This study was carried out to investigate whether shark hepatic stimulator substance (HSS) can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide (TAA)-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA (400 mg/kg) in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS (80 mg/kg) 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.

Neuroprotective Role of Coenzyme Q10 against Dysfunction of Mitochondrial Respiratory Chain at Rostral Ventrolateral Medulla during Fatal Mevinphos Intoxication in the Rat

We evaluated the functional changes in the mitochondrial respiratory chain at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, in an experimental model of fatal organophosphate poisoning using the insecticide mevinphos (Mev). We also investigated the neuroprotective role of coenzyme Q10 (CoQ10) in this process. Intravenous administration of Mev (1 mg/kg) in Sprague-Dawley rats maintained with propofol elicited an initial hypertension followed by hypotension, accompanied by bradycardia, with death ensuing within 10 min. Enzyme assay revealed a significant depression of the activity of nicotinamide adenine dinucleotide cytochrome c reductase, succinate cytochrome c reductase, and cytochrome c oxidase in the RVLM during this fatal Mev intoxication. ATP production also underwent a significant decrease. Pretreatment by microinjection bilaterally of CoQ10 (4 microg) into the RVLM significantly prevented mortality, antagonized the cardiovascular suppression, and reversed the depressed mitochondrial respiratory enzyme activities, or reduced ATP production in the RVLM induced during Mev intoxication. Our results indicated that dysfunction of mitochondrial respiratory chain and energy production at the RVLM takes place during fatal Mev intoxication. We further demonstrated that CoQ10 provides neuroprotection against Mev-induced cardiovascular depression and fatality through maintenance of activity of the key mitochondrial respiratory enzymes in the RVLM.

Update on Chronic Progressive External Ophthalmoplegia

Mitochondrial encephalomyopathies are clinically and genetically heterogeneous disorders. External ophthalmoplegia is the most frequent symptom. Other frequently involved tissues and organs include the retina, heart, limb muscles, peripheral and central nervous system, inner ear and endocrine system. The diagnosis is based on the finding of elevated serum lactate, the characteristic histopathological changes in the muscle biopsy, and decreased activities of mitochondrial respiratory chain enzymes. In many cases, the underlying molecular defect in the mtDNA can be identified. The efficacy of pharmacological therapies (e.g., coenzyme Q) has not been established so far. Symptomatic ophthalmological treatment includes ptosis and strabismus surgery. Early cardiac pacemaker implantation may be life-saving.

Mitochondrial dysfunction and ultrastructural damage in the hippocampus during kainic acid-induced status epilepticus in the rat.

Prolonged and continuous epileptic seizure (status epilepticus) results in cellular changes that lead to neuronal damage. We investigated whether these cellular changes entail mitochondrial dysfunction and ultrastructural damage in the hippocampus, by using a kainic acid (KA)-induced experimental status epilepticus model. In Sprague-Dawley rats maintained under chloral hydrate anesthesia, KA (0.5 nmol) was microinjected unilaterally into the CA3 subfield of the hippocampus to induce seizure-like hippocampal EEG activity. The activity of key mitochondrial respiratory chain enzymes in the dentate gyrus (DG), or CA1 or CA3 subfield of the hippocampus was measured 30 or 180 min after application of KA. Ultrastructure of mitochondria in those three hippocampal subfields during KA-induced status epilepticus also was examined with electron microscopy. Microinjection of KA into the CA3 subfield of the hippocampus elicited progressive build-up of seizure-like hippocampal EEG activity. Enzyme assay revealed significant depression of the activity of nicotinamide adenine dinucleotide cytochrome c reductase (marker for Complexes I+III) in the DG, or CA1 or CA3 subfields 180 min after KA-elicited temporal lobe status epilepticus. Conversely, the activities of succinate cytochrome c reductase (marker for Complexes II+III) and cytochrome c oxidase (marker for Complex IV) remained unaltered. Discernible mitochondrial ultrastructural damage, varying from swelling to disruption of membrane integrity, also was observed in the hippocampus 180 min after hippocampal application of KA. Our results demonstrated that dysfunction of Complex I respiratory chain enzyme and mitochondrial ultrastructural damage in the hippocampus are associated with prolonged seizure during experimental temporal lobe status epilepticus.

Evidence for chronic mitochondrial impairment in the cervical spinal cord of a murine model of motor neuron disease

Profound alteration of the oxygen consumption rate (QO2) is present in the cervical spinal cord (CS) of the wobbler mice aged 12 weeks (wr12). Early symptomatic mice at 4 weeks (wr4) show less pronounced changes with decreases of basal QO2 (P < 0.03) and of QO2 through complex I (P < 0.04). Mitochondrial respiratory enzyme activities, measured spectrophotometrically in the CS homogenate, show no difference between wr12 and controls, whereas complex I is reduced in the wr4 CS (P < 0.0003). Complex I activity is lower than normal both in wr12 and wr4 CS when measured in motor neurons by mean of a histochemical technique. Electron microscopy (EM) reveals a mixture of normal and morphologically altered mitochondria in wr4 motor neurons. The wobbler lumbar spinal cord is spared even at 12 weeks. Our results demonstrate the presence of mitochondrial abnormalities in the wobbler CS since the first manifestations of the disease. Thus, chronic mitochondrial dysfunction has a contributory role in motor neuron degeneration in the wobbler disease.

Coq7/clk-1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q.

coq7/clk-1 was isolated from a long-lived mutant of Caenorhabditis elegans, and shows sluggish behaviours and an extended lifespan. In C. elegans and Saccharomyces cerevisiae, coq7/clk-1 is required for the biosynthesis of coenzyme Q (CoQ), an essential co-factor in mitochondrial respiration. The clk-1 mutant contains dietary CoQ(8) from Escherichia coli and demethoxyubiquinone 9 (DMQ9) instead of CoQ(9). In a previous study, we generated COQ7-deficient mice by targeted disruption of the coq7 gene and reported that mouse coq7/clk-1 is also essential for CoQ synthesis, maintenance of mitochondrial integrity and neurogenesis. In the present study, we rescued COQ7-deficient mice from embryonic lethality and established a mouse model with decreased CoQ level by transgene expression of COQ7/CLK-1. A biochemical analysis showed a concomitant decrease in CoQ(9), mitochondrial respiratory enzyme activity and the generation of reactive oxygen species (ROS) in the mitochondria of CoQ-insufficient mice. This implied that the depressed activity of respiratory enzymes and the depressed production of ROS may play a physiological role in the control of lifespan in mammalian species and of C. elegans.

Mitochondrial damage and metabolic compensatory mechanisms induced by hyperoxia in the U-937 cell line.

Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% O(2), 96 h culture) to induce oxidative stress in the human leukemia cell line, U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.

In vivo TNF-alpha inhibition ameliorates cardiac mitochondrial dysfunction, oxidative stress, and apoptosis in experimental heart failure.

Heart failure is associated with increased myocardial expression of TNF-alpha. However, the role of TNF-alpha in the development of heart failure is not fully understood. In the present study, we investigated the contribution of TNF-alpha to myocardial mitochondrial dysfunction, oxidative stress, and apoptosis in a unique dog model of heart failure characterized by an activation of all of these pathological processes. Male mongrel dogs were randomly assigned (n = 10 each) to 1) normal controls; 2) chronic pacing (250 beats/min for 4 wk) with concomitant administration of etanercept, a soluble p75 TNF receptor fusion protein, 0.5 mg/kg subcutaneously twice weekly; 3) chronic pacing with administration of saline vehicle. Mitochondrial function was assessed by left ventricular (LV) tissue mitochondrial respiratory enzyme activities. Oxidative stress was assessed with aldehyde levels, and apoptosis was quantified by photometric enzyme immunoassay for cytoplasmic histone-associated DNA fragments and terminal deoxynucleotide transferase-mediated nick-end labeling (TUNEL) assays. LV activity levels of mitochondrial respiratory chain enzyme complex III and V were reduced in the saline-treated dogs and restored either partially (complex III) or completely (complex V) in the etanercept-treated dogs. Aldehyde levels, DNA fragments, and TUNEL-positive cells were increased in the saline-treated dogs and normalized in etanercept-treated dogs. These changes were accompanied by an attenuation of LV dilatation and partial restoration of ejection fraction. Our data demonstrate that TNF-alpha contributes to progressive LV dysfunction in pacing-induced heart failure, mediated in part by a local impairment in mitochondrial function and increase in oxidative stress and myocyte apoptosis.

Depression of mitochondrial respiratory enzyme activity in rostral ventrolateral medulla during acute mevinphos intoxication in the rat.

We investigated possible changes in bioenergetics at the rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts to elicit cardiovascular intoxication. In Sprague-Dawley rats maintained under propofol anesthesia, microinjection bilaterally of Mev (10 nmol) into the RVLM induced progressive hypotension that was accompanied by an early augmentation (80-100 min post-Mev; Phase I), followed by a decrease (>100 min post-Mev; Phase II) in the power density of the vasomotor components (0-0.8 Hz) in systemic arterial pressure (SAP) signals. Enzyme assay revealed that local application of Mev into the RVLM also significantly and progressively depressed the activity of NADH cytochrome c reductase (marker for Complexes I and III) and cytochrome c oxidase (marker for Complex IV) in the mitochondrial respiratory chain of the RVLM, but not the heart. On the other hand, the activity of succinate cytochrome c reductase (marker for Complexes II and III) remained unaltered. Both the cardiovascular consequences and depression of mitochondrial respiratory chain enzymes elicited by Mev were significantly antagonized on comicroinjection of atropine (3.5 or 7 nmol) bilaterally into the RVLM. We conclude that Mev adversely effects cardiovascular control by acting as a cholinesterase inhibitor in the RVLM, whose neuronal activity is intimately related to the death process. The resulting accumulation of acetylcholine and prolonged activation of muscarinic receptors in the RVLM is manifested by a selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain that underlies cardiovascular toxicity associated with organophosphate poisons such as Mev.

Mitochondrial complex I and IV activities in leukocytes from patients with parkin mutations.

The parkin protein functions as a RING-type ubiquitin protein ligase. Considering the possibility that impaired ubiquitin-proteosomal system activity may impair antioxidant defenses and enhance oxidative stress, we have investigated the activity of mitochondrial respiratory enzymes in patients with parkin gene mutations. A significant decrease in the leukocyte complex I activity was found both in patients with parkin mutations (62.5%) and idiopathic PD (64.5%) compared with age-matched controls (P < 0.001). Complex IV activity was also decreased significantly in idiopathic PD patients (60%), but no difference was detected between controls and patients with parkin mutations.

Short communication: reversible mitochondrial respiratory chain impairment during symptomatic hyperlactatemia associated with antiretroviral therapy.

Direct evidence confirming the hypothesis that a dysfunction of the mitochondrial respiratory chain (MRC) underlies the pathogenesis of hyperlactatemia associated with highly active antiretroviral therapy (HAART) is scarce. We studied mitochondrial DNA (mtDNA) content and MRC function in the skeletal muscle of an HIV-infected patient during an episode of symptomatic hyperlactatemia. Skeletal muscle biopsy was performed during the episode when the patient was symptomatic and 3 months later when the patient was clinically recovered. Assessment of mitochondria was performed using histological, polarographic, spectrophotometrical, and Southern blot and real time PCR DNA quantification methods. The histological study disclosed extensive mitochondrial impairment in the form of ragged-red fibers or equivalents on oxidative reactions. These findings were associated with an increase in mitochondrial content and a decrease in both mitochondrial respiratory capacity and MRC enzyme activities. Mitochondrial DNA content declined to 53% of control values. Mitochondrial abnormalities had almost disappeared later when the patient became asymptomatic. Our findings support the hypothesis that MRC dysfunction stands at the basis of HAART-related hyperlactatemia.

Cardiac mitochondrial complex activity is enhanced by heat shock proteins.

1. Prolonged ischaemia and reperfusion in heart transplantation results in mitochondrial dysfunction and loss of cardio-energetics. Improved myocardial tolerance to ischaemia-reperfusion can be increased by de novo synthesis of heat shock protein (Hsp) groups, transiently expressed following mild hyperthermic or oxidative stress. Consideration of the roles of various Hsp in ischaemic-reperfused myocardium can provide new insights into potential therapeutic adjuncts to cardiac surgery. 2. Several Hsp classes have been located within or in association with mitochondrial elements. Cardiac Hsp research has focused primarily on the 70 kDa group, involved in protein folding functions within the cytosol and matrix. Similarly, Hsp 60 and 10 have been shown to form a mitochondrial chaperonin complex conferring protection to ischaemia-challenged myocytes. Equally pertinent is Hsp 32, an isoform of the haem-metabolizing enzyme heme oxygenase. 3. Our studies have shown that mitochondrial respiratory enzyme activity can be protected by Hsp, affording protection to cardiac energetics during preservation for transplantation. Upregulation of Hsp 32, 60 and 72 in rats, achieved by mild hyperthermic stress, improved cardiac function, ultrastructure and mitochondrial respiratory and complex activities in ex vivo perfused hearts subjected to cold cardioplegic arrest and ischaemia-reperfusion. Pre-ischaemic mitochondrial complex activities were increased in heat stress versus sham-treated groups for complex I, IV and V. 4. Investigation of the direct effect of upregulation of Hsp 72 by gene transfection resulted in a similar pattern of response, with increased complex I activity and improved ventricular function. 5. These studies provide the first evidence of Hsp-mediated enhancement of mitochondrial energetic capacity. Enhanced protection of mitochondrial energetics, as a result of increased Hsp expression, contributes to the recovery of myocardial function in ischaemia-reperfusion.

Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome.

A group of 12 children clinically presenting with hypotonia, intractable epilepsy, autism, and developmental delay, who did not fall into previously described categories of mitochondrial encephalomyopathy, were evaluated for mitochondrial respiratory enzyme activity levels, mitochondrial DNA, and mitochondrial structural abnormalities. Reduced levels in specific respiratory activities were found solely in enzymes with subunits encoded by mitochondrial DNA in seven of eight biopsied skeletal muscle specimens evaluated. Five cases exhibited increased levels of large-scale mitochondrial DNA deletions, whereas pathogenic point mutations previously described in association with mitochondrial encephalomyopathies were not found. Mitochondrial structural abnormalities were present in three of four patients examined. Our findings suggest that mitochondrial dysfunction, including extensive abnormalities in specific enzyme activities, mitochondrial structure, and mitochondrial DNA integrity, may be present in children with a clinical constellation including hypotonia, epileptic seizures, autism, and developmental delay. The acronym HEADD is presented here to facilitate pursuit of mitochondrial defects in patients with this clinical constellation after other causes have been excluded.

The iron-loaded gerbil model revisited: Effects of deferoxamine and deferiprone treatment

Although the beneficial effects of deferoxamine (DFO) on iron-associated morbidity and mortality are well documented, the role of deferiprone (L1) in the management of transfusional iron overload is controversial. This debate involves not only the question of efficacy but also of safety, with particular emphasis on the risk of a paradoxical aggravation of iron toxicity by L1. We used the iron-loaded gerbil model introduced by Carthew et al to compare the chelating efficacy of L1, DFO, or both in two gerbil strains treated by means of weekly iron-dextran injections: Psammomys obesus and pathogen-free Mongolian gerbils (Meriones unguiculatus). The difference between the high mortality and advanced hepatocellular necrosis observed in iron-loaded P obesus and the absence of mortality and limited morbidity encountered in pathogen-free Mongolian gerbils is most likely explained by the prevention of coincidental laboratory infections in the latter group. Iron-chelating treatment in all experimental groups resulted in a significant decrease in hepatic iron concentrations and normalization of mitochondrial respiratory enzyme activities, with combined L1 and DFO treatment being the most efficient, followed, in decreasing order, by DFO and L1 as single-drug treatments. Judged by tissue iron concentrations, mitochondrial enzyme activity, and hepatic histology, we could find no evidence of a paradoxical aggravation of iron toxicity by L1 in either of the two series of studies. Although these data appear to be reassuring, the present controversy related to the role of L1 in the development of hepatic cirrhosis should be eventually settled by clinical studies evaluating the effects of long-term iron-chelating treatment. (J Lab Clin Med 2002;139:50-8)

Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure.

Previous studies have shown that marked changes in myocardial mitochondrial structure and function occur in human cardiac failure. To further understand the cellular events and to clarify their role in the pathology of cardiac failure, we have examined mitochondrial enzymatic function and peptide content, and mitochondrial DNA (mtDNA) integrity in a canine model of pacing-induced cardiac failure. Myocardium and skeletal muscle tissues were evaluated for levels of respiratory complex I-V and citrate synthase activities, large-scale mtDNA deletions as well as peptide content of specific mitochondrial enzyme subunits. Levels of circulating and cardiac tumor necrosis factor-alpha (TNF-alpha), and of total aldehyde content in left ventricle were also assessed. Specific activity levels of complex III and V were significantly lower in both myocardial and skeletal muscle tissues of paced animals compared to controls. In contrast, activity levels of complex I, II, IV and citrate synthase were unchanged, as was the peptide content of specific mitochondrial enzyme subunits. Large-scale mtDNA deletions were found to be more likely present in myocardial tissue of paced as compared to control animals, albeit at a relatively low proportion of mtDNA molecules (<0.01% of wild-type). In addition, the reduction in complex III and V activities was correlated with elevated plasma and cardiac TNF-alpha levels. Significant increases in left ventricle aldehyde levels were also found. Our data show reductions in specific mitochondrial respiratory enzyme activities in pacing-induced heart failure which is not likely due to overall decreases in mitochondrial number, or necrosis. Our findings suggest a role for mitochondrial dysfunction in the pathogenesis of cardiac failure and may indicate a commonality in the signaling for pacing-induced mitochondrial dysfunction in myocardial and skeletal muscle. Increased levels of TNF-alpha and oxidative stress appear to play a contributory role.

Mouse CLK-1 Is Imported into Mitochondria by an Unusual Process That Requires a Leader Sequence but No Membrane Potential

clk-1 has been identified and characterized in the nematode Caenorhabditis elegans as a gene that affects the rates, regularity, and synchrony of physiological processes. The CLK-1 protein is mitochondrial and is required for ubiquinone biosynthesis in yeast and in worms, but its biochemical function remains unclear. We have studied the expression of murine mclk1 in a variety of tissues, and we find that the pattern of mclk1 mRNA accumulation closely resembles that of mitochondrial genes involved in oxidative phosphorylation. The pattern of protein accumulation, however, is sharply distinct in some tissues; mCLK1 appears relatively enriched in the gut and depleted in the nervous tissue. We also show that mCLK1 is synthesized as a preprotein that is imported into the mitochondrial matrix, where a leader sequence is cleaved off and the protein becomes loosely associated with the inner membrane. However, in contrast to all known mitochondrial proteins that contain a cleavable pre-sequence, the import of mCLK1 does not require a mitochondrial membrane potential.

Heat Stress Contributes to the Enhancement of Cardiac Mitochondrial Complex Activity

Hyperthermic stress is known to protect against myocardial dysfunction after ischemia-reperfusion injury. It is unclear however, what energetic mechanisms are affected by the molecular adaptation to heat stress. We hypothesized that mild hyperthermic stress can increase mitochondrial respiratory enzyme activity, affording protection to mitochondrial energetics during prolonged cardiac preservation for transplantation. Rat hearts were excised after heat-stress or sham treatment and subjected to cold cardioplegic arrest and ischemia followed by reperfusion in an ex vivo perfusion system. Cardiac function, mitochondrial respiratory, and complex activities were assessed before and after ischemia. Heat shock protein (Hsp 32, 60, and 72) expression was increased in heat-stressed hearts. This was associated with increased mitochondrial complex activities in heat-stress versus sham-treated groups for complex I-V. During reperfusion, higher complex activities and respiratory control ratios were observed in heat-stressed versus sham-treated groups. Recovery of ventricular function was improved in heat-stressed hearts. Furthermore, mitochondria in reperfused heat-stressed myocardium exhibited intact membranes with packed, parallel, lamellar cristae, whereas in sham-treated myocardium, mitochondria were severely disrupted. This study provides the first evidence of heat-stress-mediated enhancement of mitochondrial energetic capacity. This is associated with increased tolerance to ischemia-reperfusion injury. Protection by heat stress against myocardial dysfunction may be partially due to enhancement of mitochondrial energetics.

Inhibition of Mitochondrial Lipid Peroxidation by Bakuchiol, a Meroterpene from Psoralea corylifolia

Bakuchiol, a meroterpene isolated from Psoralea corylifolia, prevented mitochondrial lipid peroxidation. Inhibition of oxygen consumption originating in lipid peroxidation was time-dependent. Bakuchiol protected mitochondrial respiratory enzyme activities against both NADPH-dependent and dihydroxyfumarate-induced peroxidation injury. Bakuchiol was shown to be effective to protect mitochondrial functions against oxidative stress.