Red Muscle Fibers Research Articles

Insulin Resistance of Skeletal Muscle during Pregnancy is not a Consequence of Intrinsic Modifications of Insulin Receptor Binding or Kinase Activities*

Insulin action in skeletal muscle is markedly depressed at late pregnancy. The purpose of this study was to investigate whether insulin resistance of skeletal muscle during pregnancy is associated to intrinsic alterations in the biological activities of insulin receptor. To that end, insulin receptors from mixed, red and white skeletal muscle from control and 19-20 days pregnant rats were partially purified and insulin binding and tyrosine kinase activities were evaluated. Muscle insulin receptors from diabetic rats were also studied provided that changes in receptor number and tyrosine kinase activities had been clearly substantiated. Total high affinity insulin binding sites expressed either per gram of tissue or per milligram of protein were similar in muscles from control and pregnant rats, in contrast to diabetic rats in which an increased high affinity receptor number was observed. No differences in affinity were detected for high affinity binding sites in any of the groups investigated. The integrity of the partially purified insulin receptors from control and pregnant groups was identical as determined by affinity cross-linking of [125I-TyrB26]insulin to the receptor and by beta-subunit phosphorylation. Autophosphorylation of the beta-subunit and the pattern of phosphopeptides obtained after digestion of phosphorylated beta-subunit with trypsin, elastase, and staphylococcal V8 protease were indistinguishable in control and pregnant groups. Tyrosine receptor kinase was also similar in receptor preparations from control and pregnant muscle. This is in contrast to diabetes in which a defective tyrosine kinase was confirmed. In order to detect possible differences due to the fiber type, further sets of experiments were performed in receptor preparations from red and white muscle. In keeping with previous data, tyrosine kinase activity of the insulin receptor was 2.5-fold greater in red muscle than white muscle; however, under these conditions, receptor kinase activity was unmodified in preparations from pregnant rats in red and white muscle fibers. Recent evidence has revealed the existence of an insulin binding inhibitor in muscle extracts. We detected the presence of such an inhibitor in the flow-through fraction after WGA chromatography. This inhibitory activity was found to be greater in muscle extracts obtained from pregnant rats as compared to fractions from control rats. We conclude that insulin resistance of skeletal muscle at late pregnancy is not explained by intrinsic modifications of insulin receptor binding or kinase activities.(ABSTRACT TRUNCATED AT 400 WORDS)

Hyperplasia and hypertrophy in the growth of skeletal muscle in juvenile Atlantic salmon, Salmo salar L.

Both red and white muscle fibre numbers in juvenile Atlantic salmon increased gradually with fish length throughout the freshwater growth period. Mean fibre area increased as fish grew to 6.5 cm f.l., but thereafter was unrelated to fish length. Hyperplasia was most obvious when fish were growing fastest, and was the dominant growth process in fish over 6.5 cm f.l. Hypertrophy was most important when growth was slow, as in autumn and winter.Mean white fibre area was significantly smaller in deep muscle than at medial and superficial sites. Total cross‐sectional area of red, white and total trunk muscle increased with fish length. The ratio of red: white cross‐sectional area increased with fish length to a plateau at about 10% after 6.5 cm f.l.

The histochemistry of muscle in juvenile Atlantic salmon, Salmo solar L.

In fry, 1‐ and 2‐year old juvenile Atlantic salmon, relatively small superficial red muscle fibres staining well for glycogen and succinic dehydrogenase (SDH) but with little myofibrillar ATPase, were evident on either side of the lateral line, in June. Well differentiated relatively large white fibres contained lower concentrations of glycogen than the red fibres, higher ATPase and no SDH, except traces in the larger 1‐ and 2‐year‐olds. Intermediate size pink fibres, which were also intermediate between red and white fibres in their staining properties, occurred in a thin diffuse layer along the red‐white boundary, thickest at the apex near the vertebral column, and most evident in the younger fish.

Identification of motoneurons in the spinal cord of the zebrafish (Brachydanio rerio), with special reference to motoneurons that innervate intermediate muscle fibers

We investigated the location and size distribution of motoneurons that innervate red, intermediate and white muscle fibers in the axial musculature of the zebrafish (Brachydanio rerio). Motoneurons were identified by retrograde labeling from the respective myotomal compartments with horseradish peroxidase applied either in small polyacrylamide gel fragments or as pure crystals. We found a spatial relationship between the three myotomal muscle fiber types and the corresponding motoneurons. The white motoneurons are grouped in the dorsal part of the motorcolumn, near the central canal. Motoneurons of the red and intermediate muscle are clustered in the ventral part of the motorcolumn. The average position of the red motoneurons is ventral to that of the intermediate motoneurons. Some sizes are distributed over wide overlapping ranges, spanning from 41 to 352 microns 2 for red and intermediate and from 56 to 894 microns 2 for white motoneurons. These data are discussed in relation to the recruitment order of myotomal muscle fibers of different types as revealed by electromyographic recordings in fish, and the so called "size principle" for motoneuron recruitment.

Lactate: a substrate for reptilian muscle gluconeogenesis following exhaustive exercise

The pattern of lactate and glycogen metabolism in red and white muscle fibers was examined in fasted, cannulated lizards (Dipsosaurus dorsalis) run on a treadmill to exhaustion. The white and red portions of the iliofibularis (wIF, rIF) muscle of the hindlimb were analyzed post-exercise and at intervals over 120 min of recovery for lactate and glycogen changes. Five min of exercise resulted in lactate concentrations of from 35 mM (rIF) to 48 mM (wIF) while blood lactate concentrations were elevated to 21 mM from resting levels of 1.8 mM. Glycogen depletion was significant (p<0.05) in whole hindlimb (−30%) and in wIF (−42%) but not in rIF (−25%). Metabolite changes were consistent with a pattern of fiber type recruitment favoring fast-twitch glycolytic (FG) fibers during high intensity locomotion. Glycogen replenishment during recovery was fiber typespecific. After 2 h recovery, whole hindlimb glycogen concentration had increased 24% above pre-exercise levels (p<0.05). Rates of glycogen resynthesis during recovery were significant only in oxidative fibers of the red iliofibularis. Animals were infused with either [U-14C]-lactate or [U-14C]-glucose at the point of exhaustion, and label incorporation into muscle glycogen was used to estimate the substrate preference for glycogenesis during recovery. Lactate uptake and incorporation occurred in both wIF and rIF. Glucose uptake and incorporation into glycogen was greatest in the rIF, where it equalled 9% of the rate of lactate incorporation. The rate of lactate incorporation could account for 67% of the rate of glycogen synthesis that occurred in oxidative fibers of the rIF. The data indicate that in contrast to mammalian muscle, reptilian muscle replenishes glycogen while it removes lactate, utilizing lactate directly as a gluconeogenic substrate. The data also suggest that lactate produced by FG fibers during exercise is utilized by oxidative fiber types post-exercise to synthesize glycogen in excess of pre-exercise levels.

COMPOSITION AND QUALITY OF BEEF FROM STEERS SIRED BY PIEDMONTESE, GELBVIEH AND RED ANGUS BULLS1

Abstract Forty-five steers produced by matings of Piedmontese (P), Gelbvieh (G) and Red Angus (RA) sires to British (B) and Continental crossbred (Cx) dams were started on a finishing diet at an average of 291 d. Five steers from each sire-breed group were slaughtered after 124, 166 or 208 d of finishing. Age-constant values for slaughter weight and estimated degree of maturity did not differ for the three sire breed groups. Carcasses produced by P steers had the least fat thickness, the largest longissimus muscle (LM) areas, the lowest numerical yield grades, the highest yields of separable muscle and the highest muscle-to-bone ratios. Additionally, LM samples from P-sired steers had the highest percentage of white muscle fibers, the lowest percentage of intermediate muscle fibers and the smallest cross-sectional area of red muscle fibers. Marbling scores and intramuscular lipid content were highest for RA steers; P and G steers had similar values for marbling and intramuscular lipid content. Longissimus steaks from G steers received the lowest ratings for tenderness, flavor intensity and amount of connective tissue. Steaks from P and RA steers received similar sensory panel ratings. No differences were observed among the three sire-breed groups for amount and solubility of intramuscular collagen or for partitioning of separable carcass fat.

Histochemistry, innervation, capillary density, and mitochondrial volume of red and white muscle fibers isolated from a lizard, Varanus exanthematicus

Fiber types in the iliofibularis muscle of the savannah monitor lizard, Varanus exanthematicus, have been characterized on the basis of their histochemical characteristics and nerve endings. Four types of fibers were identified, three of which were focally innervated and the other, multiply innervated. They corresponded to the fast glycolytic, fast oxidative glycolytic, slow oxidative, and tonic fiber types of other lower vertebrates. The fibers isolated from the white and most of the fibers from the red regions had well defined end plates. However, 15 to 20% of the fibers isolated from the red region possessed an average of 17 ± 0.5 end plates per fiber. These end plates were placed 922 ± 54 μm apart and poorly defined. The mitochondrial volume of fibers isolated from the red region (12 ± 0.5%) was six times that of fibers isolated from the white region (2 ± 0.1%). Myofibrillar volumes were similar in fibers isolated from the two regions (81 ± 0.6%, white; 77 ± 0.2%, red). However, the capillary density of fibers from the red region (932 ± 64/mm2) was four and one-half times that of fibers isolated from the corresponding white region (200 ± 35/mm2).

The fine structure of muscle fibres of roach, Rutilus rutilus (L.), and chub, Leuciscus cephalus (L.), Cyprinidae, Teleostei: interspecific differences and effects of habitat and season

Red and white axial muscle fibres from roach and chub were investigated by electron microscopy. Fish from three different localities were compared. Qualitative and quantitative analysis of myofibrils, mitochondria, lipid and subsarcolemmal cytoplasm with regard to muscle fibre type, species, season and habitat were made. Muscle fibre types differ significantly with the exception of the subsarcolemmal cytoplasm in roach. Within‐species lipid content of red fibres differs between seasons. However, the most marked effect on red muscle fibres within species and season as regards volume density of lipid and mitochondria can be attributed to the different localities. The results are discussed in relation to mode of life and differences in habitat.

ニシン仔稚魚の体側筋の発達と遊泳速度の変化

A morphometric analysis was made of myotomal musculature, together with the measure-ment of the burst swimming speeds in Pacific herring larvae and juveniles. The frequency distribution of white muscle diameter showed that mean fiber diameter increased gradually with development but new small fibers, clearly differing from primitive fibers, were added from about 20mm SL (standard length) to 30mm SL. The diameters of red muscle fibers, however, rather continuously increased with development. The logarithmic plots of cross-sectioned area of white and red muscle against the standard length showed that both relationships in white and red muscle had two regression lines with one inflection point at 30.4mm SL and at 20.1mm SL, re-spectively. The relationships between log estimated fiber numbers of red muscle against log SL had also two regression lines with one inflection point at 24.1mm, whereas those in white muscle had two inflection point at 15.4mm and at 26.9mm. Swimming speed increased exponentially with development, but the relation between log swimming speed (V) and log standard length (L) differed from about 28mm SL (p<0.005):V=0.63L exp (1.04) and V=1.55L exp (0.90). The length in 28mm SL was fit for the changes of morphometry mentioned above in white muscle. This suggested that the maximum swimming speed may be correlated with the development of myotomal musculature, at least in the white muscle.

Function of red axial muscles of carp (Cyprinus carpio): recruitment and normalized power output during swimming in different modes

This paper offers an analysis of the recruitment and normalized power output of the slow oxidative (red) axial muscles of the carp, during swimming in two different modes. Recruitment patterns of the muscle fibres and swimming movements were measured by synchronized electromyography and cinematography. The ultrastructure of the muscle fibres along the trunk was measured by electron microscopy. Strain fluctuations and normalized power along the trunk were estimated using a model, as direct measurement was impossible. The model takes into account structural parameters of the sarcomeres, modulation of sarcomere force as a result of changing sarcomere length, modulation of cross‐bridge force owing to the force‐velocity relationship, and rate of tension rise and of tension decline as a result of fibre properties and stimulation. In continuous swimming, the amplitude of the fluctuations in the strain was constant along the trunk, owing to a remarkable coherence between the amplitude of body curvature and the position along the body of the red muscle fibres with respect to the vertebral column. However, the strain range and speed of contraction at which the fibres were active changed along the trunk in continuous swimming as well as in ‘kick and glide swimming’. During continuous swimming, the fibres along the trunk had a period of negative active power production followed by a period of positive power production. Anteriorly, the positive phase was most important, with a close to optimal power production in a plateau phase, so that net positive work was produced in a swimming cycle. Posteriorly, net negative work was done. In the anal region, the amounts of positive and negative work almost balanced each other. During the first tail strike in intermittent swimming, peak positive normalized work for an activated fibre was produced in the anal region. For this initial tail strike, fast muscle fibres were calculated to work more effectively than slow fibres. Fast fibres were needed to generate kick and glide swimming.

31P NMR study of phosphorus metabolites in fast and slow muscles

1. 1. 31P NMR was used to characterize phosphate pools in perchloric acid extracts of muscles with various composition of muscle fibre types. 2. 2. The white m. pectoralis major (MPM) of chickens 15 min post mortem is characterized by 1.6-times higher relative content of phosphocreatine (PCr) m comparison with mixed leg muscle (LM) of this species. The glycerophosphorylcholine (GPC) does not occur in MPM at NMR detectable level in contrast to the leg muscles. Relative amounts of other phosphates are similar in both muscles. 3. 3. The intermediate MPM of pigeons as well as mixed LM of this species contain 15 min post mortem a very small amount of PCr and ATP but a large amount of inorganic phosphate. Relative content of GPC is higher in leg muscles than in intermediate MPM. 4. 4. Muscles with higher occurrence of white fibres contain relatively more PCr than muscles with lower occurrence of white fibres. 5. 5. The occurrence of GPC seems to be connected with metabolism of red muscle fibres.

Carcass, muscle and meat characteristics of lean and obese pigs.

Six pigs obtained from a lean selected strain and six pigs obtained from an obese selected strain were slaughtered at about 110 kg live-animal weight. Carcasses were evaluated; hams were dissected into bone, skin, fat and lean, and loin samples were obtained for fiber type characteristics, percentage of fat and moisture, collagen analysis, sensory characteristics, textural properties and objective color analysis. Carcasses from lean pigs were longer, had less backfat and larger longissimus muscle cross-sectional areas than carcasses obtained from obese pigs. Hams from lean pigs had less fat, more bone and more lean than hams from carcasses of obese pigs. The percentages and cross-sectional areas of red and white muscle fibers of the longissimus muscle from lean and obese pigs were not different. However, lean pigs had intermediate fibers that were only 79% as large (P less than .10) as intermediate muscle fibers from obese pigs. Intermediate fibers represented only 7 and 10% of total fiber area, whereas white fibers represented 84 and 79% of total fiber area in longissimus muscle of lean and obese pigs, respectively. Overall, lean pigs tended to possess fewer fibers (-16%) per unit of area than obese pigs, indicating that total muscle fiber hypertrophy was partially responsible for the increased longissimus muscle area of the lean strain. Sensory properties of longissimus meat samples from lean and obese strains were not different. However, the shear force requirement of the longissimus samples from the lean strain were slightly, but significantly (P less than .10), higher than those from the obese strain. No differences were observed in meat color.

Profiles of enzyme activity in larvae of two cyprinid species with contrasting life styles (Cyprinidae; Teleostei)

Growth and the development of gills, muscle fibres and 10 enzymes serving different metabolic functions were studied in larvae of Rutilus rutilus (L.) and Chalcalburnus chalcoides (Agassiz, 1832). R. rutilus starts swimming and feeding one to three days after hatching, whereas in C. chalcoides this process is delayed by about 10 days. This difference in behaviour is reflected in the time‐course of growth, the differentiation of the red muscle fibres and the activity of the enzymes of aerobic energy metabolism. On the other hand, the activity of the enzymes of anaerobic energy metabolism increases steadily throughout the period of observation (up to 60 days post‐hatch), this trend being more pronounced in C. chalcoides than in R. rutilus. A weight‐independent and a weight‐dependent phase of development can be distinguished in the enzymes of aerobic energy metabolism. It is suggested that, in accord with previous findings, the early phase of locomotor activity of cyprinid larvae is fuelled mainly by aerobic processes, and that the central muscle mass of the larvae is more aerobic than the white muscle fibres of the adults. The delayed development of aerobic enzyme activity in C. chalcoides is compensated by the accelerated development of anaerobic enzyme activity, particularly of creatine kinase and lactate dehydrogenase. This difference between the two species studied suggests differences in the metabolic basis of burst activity.

Effect of prior immobilization on muscular glucose clearance in resting and running rats.

In vitro studies have shown that prior disuse impairs the glucose clearance of red skeletal muscle because of a developed insensitivity to insulin. We studied whether an impaired glucose clearance is present in vivo in 42-h immobilized muscles of resting rats and, furthermore, whether the exercise-induced increase in glucose clearance of red muscles is affected by prior immobilization. The 2-[3H]deoxy-D-glucose (2DG) bolus injection method was used to determine glucose clearance of individual muscles. At rest, glucose clearance was markedly impaired in rats with previously immobilized red muscles compared with nonimmobilized control rats (red gastrocnemius 0.46 +/- 0.02 vs. 0.99 +/- 0.08 and soleus 1.10 +/- 0.30 vs. 3.97 +/- 0.54 ml.min-1.100 g-1, P less than 0.005). During running (18 m/min), glucose clearance did not differ between muscles in previously immobilized and control rats. Insulin levels were always similar in the two groups and decreased during exercise. Intracellular nonphosphorylated 2DG was present in tissues with high glucose clearances. In conclusions, 42 h of immobilization markedly impairs glucose clearance of resting red muscle fibers in vivo. Apparently, physical inactivity in particular affects steps involved in insulin-mediated action that are not part of contraction-induced glucose uptake and metabolism. Presence of intracellular 2DG shows that separate determination of phosphorylated 2DG is necessary for accurate estimates of glucose metabolism and that accumulation of phosphorylated 2DG does not accurately reflect glucose transport.

Life styles and patterns of development of gills and muscles in larval cyprinids (Cyprinidae; Teleostei)

A morphometric study of gill structures and of the body musculature during the first weeks after hatching was carried out on larvae of six cyprinid species: Leuciscus cephalus, L. leuciscus, Rutilus rutilus, Alburnus albumus, Chondrostoma nasus and Abramis brama. In all species a unicellular layer of red muscle fibres covers the central muscle mass; this layer is of greatest extent shortly after hatching but diminishes gradually in mass by contracting towards the lateral region of the body until it merges with (or gives rise to) the adult red muscle fibres proper. There is a close relationship between the rate of differentiation of gill structures and the rate at which the larval red muscle layer disappears, the pattern of this relationship reflecting the life style of the species. The longer the larvae delay the start of their free‐swimming existence after hatching (which in A. alburnus may be as long as 10 days) the longer does the red layer of muscle fibres serve as the organ of gas exchange and the longer is gill development suppressed. It appears that the metabolism of the swimming muscles is almost entirely aerobic so long as gas exchange takes place across the whole body surface, the glycolytic capacity of the central muscle mass developing only slowly in conjunction with the switch from red layer to gills as the major respiratory organ.

Quantitation and immunocytochemical localization of ubiquitin conjugates within rat red and white skeletal muscles.

We employed solid-phase immunochemical methods to probe the dynamics of ubiquitin pools within selected rat skeletal muscles. The total ubiquitin content of red muscles was greater than that of white muscles, even though the fractional conjugation was similar for both types of muscle. The specificity for conjugated ubiquitin in solid-phase applications, previously demonstrated for an affinity-purified antibody against SDS-denatured ubiquitin, was retained when used as a probe for ubiquitin-protein adducts in tissue sections. Immunohistochemical localization revealed that differences in ubiquitin pools derived from the relative content of red (oxidative) vs white (glycolytic) fibers, with the former exhibiting a higher content of ubiquitin conjugates. Subsequent immunogold labeling demonstrated statistically significant enhanced localization of ubiquitin conjugates to the Z-lines in both red and white muscle fiber types.

Developmental transitions of myosin isoforms and organisation of the lateral muscle in the teleost Dicentrarchus labrax (L.).

In Dicentrarchus labrax (the sea bass) the differentiation of lateral muscle fibres occurs at different stages and in different ways in the superficial (red), intermediate (pink) and deep (white) regions of the myotome. At hatching the myotomes are composed of presumptive white and red fibres, the latter forming a superficial monolayer present only near the transverse septum. At this stage, differences between the fibre types are mainly ultrastructural. From their different reactions with isoform-specific antibodies to mullet myosin, and the appearance of histochemical mATPase activity, it appears that in both red and white muscle fibres there is a transition in myosin composition from an early larval form (L1R and L1W respectively) to a late larval form (L2R and L2W) and then to the isoforms typical of adult red and white muscle. The transition from L1W to L2W in the deep muscle occurs very rapidly and early in larval life (between 10 and 28 days), whereas the equivalent transition in the superficial muscle (from L1R to L2R) is a gradual process beginning in fibres near the transverse septum and spreading hypo- and epi-axially as this layer grows around the deep muscle. The definitive adult forms (AR and AW), distinguishable by the appearance of characteristic histochemical myosin ATPase activity, are present in the superficial red muscle by 80 days, but later in the deep white muscle (by 20 months), respectively. Compared to the superficial red and deep white muscle, the intermediate (pink) muscle layer first appears relatively late (80 days), but then acquires the histo- and immunohistochemical profile characteristic of the adult form much more rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

High-resolution scanning electron-microscopic studies on the three-dimensional structure of mitochondria and sarcoplasmic reticulum in the different twitch muscle fibers of the frog.

The three-dimensional structure of the mitochondria and sarcoplasmic reticulum (SR) in the three types of twitch fibers, i.e., the red, white and intermediate skeletal muscle fibers, of the vastus lateralis muscle of the Japanese meadow frog (Rana nigromaculata nigromaculata Hallowell) was examined by high resolution scanning electron microscopy, after removal of the cytoplasmic matrices. The small red fibers have numerous mitochondrial columns of large diameter, while the large white fibers have a small number of mitochondrial columns of small diameter. In the medium-size intermediate fibers, the number and diameter of the mitochondrial columns are intermediate between those of the red and white fibers. In all three types of fibers, the terminal cisternae and transverse tubules form triads at the level of each Z-line. The thick terminal cisternae continue into much thinner flat intermediate cisternae, through a transitional part where a row of tiny indentations can be observed. Numerous slender longitudinal tubules originating from the intermediate cisternae, extend longitudinally or obliquely and form elongated oval networks of various sizes in front of the A-band, then fuse to form the H-band collar (fenestrated collar) around the myofibrils. On the surface of the H-band collar, small fenestrations as well as tiny hollows are seen. The three-dimensional structure of SR is basically the same in all three muscle fiber-types. However, the SR is sparse on the surface of mitochondria, so the mitochondria-rich red fiber has a smaller total volume of SR than the mitochondria-poor white fiber. The volume of SR of the intermediate fiber is intermediate between other the two.

Partial Characterization of the Buffering Components of the Red and White Myotomal Muscle of Marine Teleosts, with Special Emphasis on Scombrid Fishes

The buffering capacity (β) of red (RM) and white (WM) myotomal muscle fibers was measured in several species of marine teleost fishes chosen to represent a broad range of locomotory ability and anaerobic capacity. WM β differed significantly among species and correlated with WM anaerobic capacity (lactate dehydrogenase activity). Tunas had the highest WM β, deep-sea fishes had the lowest β, and there were significant differences between tuna and ectothermic species in the same family (Scombridae). WM β was significantly greater than RM β. RM β did not differ intraspecifically. The components that contribute to muscle β were partially characterized by dialyzing muscle homogenates to remove all low-MW (<2,000 daltons) buffers. Thus, β caused by lowMW buffers and the protein-specific buffering capacity were estimated. Low-MW buffers contributed 48% and 67% to total β in RM and WM, respectively. Interspecific differences in WM β were due mainly to differences in low-MW buffers, but also proteins contributed m...

Induction of an increase in mitochondrial matrix enzymes in muscle of iron-deficient rats.

Young rats maintained on an iron-deficient diet developed severe anemia and had large decreases in the levels of the iron-containing flavoproteins and cytochromes of the mitochondrial respiratory chain in skeletal muscle. In contrast, the levels of a number of mitochondrial matrix marker enzymes, including citrate synthase, isocitrate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacid-CoA transferase, and aspartate aminotransferase, increased in red skeletal muscle but not in white muscle. Phosphocreatine concentration was decreased and inorganic phosphate concentration was increased in soleus muscle frozen in situ. We hypothesize that the increase in mitochondrial matrix enzymes reflects a stimulus to mitochondrial biogenesis in posture-maintaining and weight-bearing red muscle fibers in severely iron-deficient rats. It is our working hypothesis that this stimulus to mitochondrial biogenesis arises from mild activity of the red fibers and is due to the same perturbation in cellular homeostasis that is normally caused by vigorous exercise or hypoxia. In iron deficiency, the stimulus to mitochondrial biogenesis can induce an increase in only those enzymes not prevented from increasing by iron deficiency, resulting in formation of mitochondria of grossly abnormal composition.