scholarly journals Mitochondrial Fragmentation and Dysfunction in Type IIx/IIb Diaphragm Muscle Fibers in 24-Month Old Fischer 344 Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Alyssa D. Brown ◽  
Leah A. Davis ◽  
Matthew J. Fogarty ◽  
Gary C. Sieck
Keyword(s):  
Muscle Fibers ◽  
Volume Density ◽  
Diaphragm Muscle ◽  
Type I ◽  
Mitochondrial Fragmentation ◽  
Fiber Volume ◽  
Respiratory Capacity ◽  
Dehydrogenase Reaction ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density

Sarcopenia is characterized by muscle fiber atrophy and weakness, which may be associated with mitochondrial fragmentation and dysfunction. Mitochondrial remodeling and biogenesis in muscle fibers occurs in response to exercise and increased muscle activity. However, the adaptability mitochondria may decrease with age. The diaphragm muscle (DIAm) sustains breathing, via recruitment of fatigue-resistant type I and IIa fibers. More fatigable, type IIx/IIb DIAm fibers are infrequently recruited during airway protective and expulsive behaviors. DIAm sarcopenia is restricted to the atrophy of type IIx/IIb fibers, which impairs higher force airway protective and expulsive behaviors. The aerobic capacity to generate ATP within muscle fibers depends on the volume and intrinsic respiratory capacity of mitochondria. In the present study, mitochondria in type-identified DIAm fibers were labeled using MitoTracker Green and imaged in 3-D using confocal microscopy. Mitochondrial volume density was higher in type I and IIa DIAm fibers compared with type IIx/IIb fibers. Mitochondrial volume density did not change with age in type I and IIa fibers but was reduced in type IIx/IIb fibers in 24-month rats. Furthermore, mitochondria were more fragmented in type IIx/IIb compared with type I and IIa fibers, and worsened in 24-month rats. The maximum respiratory capacity of mitochondria in DIAm fibers was determined using a quantitative histochemical technique to measure the maximum velocity of the succinate dehydrogenase reaction (SDHmax). SDHmax per fiber volume was higher in type I and IIa DIAm fibers and did not change with age. In contrast, SDHmax per fiber volume decreased with age in type IIx/IIb DIAm fibers. There were two distinct clusters for SDHmax per fiber volume and mitochondrial volume density, one comprising type I and IIa fibers and the second comprising type IIx/IIb fibers. The separation of these clusters increased with aging. There was also a clear relation between SDHmax per mitochondrial volume and the extent of mitochondrial fragmentation. The results show that DIAm sarcopenia is restricted to type IIx/IIb DIAm fibers and related to reduced mitochondrial volume, mitochondrial fragmentation and reduced SDHmax per fiber volume.

Fiber capillarization relative to mitochondrial volume in diaphragm of shrew

2002 ◽  
Vol 93 (1) ◽  
pp. 346-353 ◽  
Author(s):  
O. Mathieu-Costello ◽  
S. Morales ◽  
J. Savolainen ◽  
M. Vornanen
Keyword(s):  
Body Mass ◽  
Fiber Surface ◽  
Volume Density ◽  
Capillary Length ◽  
Fiber Volume ◽  
Hindlimb Muscle ◽  
Mitochondrial Volume ◽  
Flight Muscles ◽  
Mitochondrial Volume Density ◽  
Sorex Minutus

The objective was to examine fiber capillarization in relation to fiber mitochondrial volume in the highly aerobic diaphragm of the shrew, the smallest mammal. The diaphragms of four common shrews [ Sorex araneus; body mass, 8.2 ± 1.3 (SE) g] and four lesser shrews ( Sorex minutus, 2.6 ± 0.1 g) were perfusion fixed in situ, processed for electron microscopy, and analyzed by morphometry. Capillary length per fiber volume was extremely high, at values of 8,008 ± 1,054 and 12,332 ± 625 mm−2 in S. araneus and S. minutus, respectively ( P= 0.012), with no difference in capillary geometry between the two species. Fiber mitochondrial volume density was 28.5 ± 2.3% ( S. araneus) and 36.5 ± 1.4% ( S. minutus; P = 0.025), yielding capillary length per milliliter mitochondria values ( S. araneus, 27.8 ± 1.5 km; S. minutus, 33.9 ± 2.2 km; P = 0.06) as high as in the flight muscle of the hummingbird and small bats. The size of the capillary-fiber interface (i.e., capillary surface per fiber surface ratio) per fiber mitochondrial volume in shrew diaphragm was also as high as in bird and bat flight muscles, and it was about two times greater than in rat hindlimb muscle. Thus, whereas fiber capillary and mitochondrial volume densities decreased with increased body mass in S. araneus compared with S. minutusSoricinae shrews, fiber capillarization per milliliter mitochondria in both species was much higher than previously reported for shrew diaphragm, and it matched that of the intensely aerobic flight muscles of birds and mammals.

scholarly journals TNFα Induces Mitochondrial Fragmentation and Biogenesis in Human Airway Smooth Muscle

2020 ◽  
Author(s):  
Philippe F. Delmotte ◽  
Natalia Marin Mathieu ◽  
Gary C. Sieck
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Mitochondrial Biogenesis ◽  
Consumption Rate ◽  
Volume Density ◽  
Mitochondrial Fragmentation ◽  
Human Airway Smooth Muscle ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
Pro Inflammatory Cytokines

In human airway smooth muscle (hASM), mitochondrial volume density is greater in asthmatic patients compared to normal controls. There is also an increase in mitochondrial fragmentation in hASM of moderate asthmatics associated with an increase in Drp1 and a decrease in Mfn2 expression, mitochondrial fission and fusion proteins, respectively. Pro-inflammatory cytokines such TNFα contribute to hASM hyperreactivity and cell proliferation associated with asthma. However, the involvement of pro-inflammatory cytokines in mitochondrial remodeling is not clearly established. In non-asthmatic hASM cells, mitochondria were labeled using MitoTracker Red and imaged in 3-D using a confocal microscope. After 24-h TNFα exposure, mitochondria in hASM cells were more fragmented, evidenced by decreased form factor, aspect ratio and increased sphericity. Associated with increased mitochondrial fragmentation, Drp1 expression increased while Mfn2 expression was reduced. TNFα also increased mitochondrial biogenesis in hASM cells reflected by increased PGC1α expression and increased mitochondrial DNA copy number. Associated with mitochondrial biogenesis, TNFα exposure also increased mitochondrial volume density and porin expression, resulting in an increase in maximum O2 consumption rate. However, when normalized for mitochondrial volume density, O2 consumption rate per mitochondrion was reduced by TNFα exposure. Associated with mitochondrial fragmentation and biogenesis, TNFα also increased hASM cell proliferation, an effect mimicked by siRNA knockdown of Mfn2 expression and mitigated by Mfn2 overexpression. The results of this study support our hypothesis that in hASM cells exposed to TNFα mitochondria are more fragmented, with an increase in mitochondrial biogenesis and mitochondrial volume density resulting in reduced O2 consumption rate per mitochondrion.

scholarly journals Oxidative capacity distribution in skeletal muscle fibers of the rat.

1994 ◽  
Vol 189 (1) ◽  
pp. 1-11 ◽  
Author(s):  
M Philippi ◽  
A H Sillau
Keyword(s):  
Muscle Fibers ◽  
Oxidative Capacity ◽  
Volume Density ◽  
The Other ◽  
Isolated Mitochondria ◽  
Interfibrillar Mitochondria ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
The Difference ◽  
Subsarcolemmal Mitochondria

To study the distribution of oxidative capacity in muscle fibers, mitochondrial volume density and the oxidative capacity of isolated mitochondria were evaluated. Mitochondria were isolated from the subsarcolemmal and interfibrillar areas of the soleus (a muscle largely made up of slow oxidative fibers) and the gastrocnemius medial head (a muscle largely made up of fast glycolytic fibers) of the rat, and their oxidative capacities were evaluated using NADH- and FADH-generating substrates. In the soleus muscle, the subsarcolemmal mitochondria showed a lower oxidative capacity than interfibrillar mitochondria when NADH-generating substrates were used. This difference was not observed when FADH-generating substrates were used. In the gastrocnemius, there were no differences in the oxidative capacity of the subsarcolemmal and the interfibrillar mitochondria. Additionally, citrate synthase activity was found to be lower in mitochondria isolated from the subsarcolemmal area of the soleus than in the other mitochondrial preparations. These findings indicate that the difference in oxidative capacity of the isolated mitochondria is not related to differences in the inner mitochondrial membranes. Mitochondrial volume density was evaluated using electron micrographs of the subsarcolemmal and interfibrillar areas of slow oxidative fibers from the soleus and fast glycolytic fibers from the gastrocnemius. In the slow oxidative fibers, mitochondrial volume density in the subsarcolemmal area was four times higher than in the interfibrillar area. In the fast glycolytic fibers, mitochondrial volume densities in the subsarcolemmal and interfibrillar areas did not differ from that of the interfibrillar area of the slow oxidative fibers. The oxidative capacity of the tissue, calculated by multiplying the mitochondrial oxidative capacities by the mitochondrial volume densities, was 2-4 times higher in the subsarcolemmal areas of the soleus fibers than in the other areas studied. This was true in spite of the fact that the oxidative capacity of the subsarcolemmal mitochondria of the slow oxidative fibers was lower than those of the other mitochondrial populations studied. These results indicate that the difference in oxidative capacity between slow oxidative fibers and fast glycolytic fibers is the result of the much greater mitochondrial volume density in the subsarcolemmal area of the slow oxidative fibers.

Fiber capillarization and ultrastructure of pigeon pectoralis muscle after cold acclimation

1998 ◽  
Vol 201 (23) ◽  
pp. 3211-3220 ◽  
Author(s):  
O. Mathieu-Costello ◽  
P. J. Agey ◽  
E. S. Quintana ◽  
K. Rousey ◽  
L. Wu ◽  
...  
Keyword(s):  
Cold Acclimation ◽  
Fiber Type ◽  
Pectoralis Major Muscle ◽  
Central Area ◽  
Volume Density ◽  
Pectoralis Muscle ◽  
Capillary Length ◽  
Fiber Volume ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density

We investigated the effect of 2 months of exposure to cold conditions(0-5 C) on capillarization and on fiber size, distribution and ultrastructure in the pectoralis muscle of nine pigeons (Columbia livia;mean body mass 700 31 g) and compared the results with measurements from four control birds (mean mass 715 42 g) kept at normal ambient temperature(22-23 C) for the same period. Superficial and deep portions of the muscles, taken from the central area of the right or left pectoralis major muscle, were perfusion-fixed in situ, processed for electron microscopy and analyzed by morphometry. Aerobic fibers represented the vast majority of fibers (93 1 %, mean s.e.m.) in all samples. After cold-acclimation, fiber sectional area was reduced and capillary density increased proportionally. There was no change in the degree of orientation (anisotropy) of capillaries, capillary-to-fiber ratio or fiber type distribution compared with controls. The volume density of mitochondria and lipid droplets in aerobic fibers and capillary diameter increased in response to cold, while the linear relationship between capillary length per fiber volume and fiber mitochondrial volume density remained unchanged. Capillary surface area,intrafiber lipid deposition and fiber mitochondrial volume density were all correlated in cold-acclimated pigeons. The results indicate a close match between the aerobic capacity of the highly aerobic fibers of the pectoralis muscle and their vascularization to meet the increased energetic demand of shivering.

Capillary–fiber geometrical relationships in tuna red muscle

1992 ◽  
Vol 70 (6) ◽  
pp. 1218-1229 ◽  
Author(s):  
Odile Mathieu-Costello ◽  
Peter J. Agey ◽  
Richard B. Logemann ◽  
Richard W. Brill ◽  
Peter W. Hochachka
Keyword(s):  
Fiber Surface ◽  
Fish Muscle ◽  
Volume Density ◽  
Capillary Length ◽  
Fiber Volume ◽  
Cross Sectional ◽  
Red Muscle ◽  
Rat Soleus Muscle ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density

The aim of this study was to examine the size and geometry of the capillary network in tuna red muscle, one of the most aerobic muscles in fish. Deep red muscle of 1.5- to 2-kg skipjack tuna, Katsuwonus pelamis, was perfusion fixed in situ, processed for electron microscopy, and analyzed by morphometry. Fiber cross-sectional area was 560 ± 30 (SE) μm2 in the samples. Capillary length per fiber volume was 4143 ± 242 (SE) mm−2 and mitochondrial volume density 28.5 ± 1.0 (SE) %. Indexes of capillarity such as average number of capillaries around a fiber, capillary length and surface per fiber volume, and capillary surface per fiber surface were high for a fish muscle. In fact, the size of the capillary–fiber interface (i.e., capillary to fiber surface) at a given mitochondrial volume per fiber was not significantly different in tuna red muscle compared with rat soleus muscle. However, calculation of mitochondrial respiratory rates in tuna red muscle yielded a substantially lower value (approximately 1/20th) compared with muscles of mammals. Besides the possible effect of differences in operating temperatures and (or) mitochondrial function(s) in fish compared with mammals, this suggests that the large capillary–fiber interface in tuna may be related to functions other than oxygen delivery per se, such as substrate and (or) heat transfer between capillaries and muscle fiber.

Muscle ultrastructure and biochemistry of lowland Tibetans

1996 ◽  
Vol 81 (1) ◽  
pp. 419-425 ◽  
Author(s):  
B. Kayser ◽  
H. Hoppeler ◽  
D. Desplanches ◽  
C. Marconi ◽  
B. Broers ◽  
...  
Keyword(s):  
Body Mass ◽  
Muscle Fiber ◽  
Volume Density ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
O2 Consumption ◽  
Muscle Ultrastructure ◽  
Mitochondrial Volume ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Mitochondrial Volume Density

Muscle ultrastructure and biochemistry in vastus lateralis muscle biopsies and the response to exercise of 8 lowland Tibetans (T) were compared with those of 8 Nepalese lowlanders (N). Blood hemoglobin was lower in T than in N (119 +/- 3 vs. 131 +/- 2 g/l; P < 0.05). Peak O2 consumption per kilogram of body mass was similar [37.9 +/- 2.2 (T) vs. 40.1 +/- 1.36 ml.min-1.kg body mass-1 (N)]. Maximum exercise blood lactate was the same [11.4 (T) +/- 0.5 vs. 11.3 +/- 0.6 mM (N)]. Muscle fiber type distribution was similar [type I, 58.6 +/- 3.4 (N) vs. 57.0 +/- 3.4% (T); type IIa, 24.1 +/- 3.5 vs. 27.1 +/- 1.6%; type IIb, 17.4 +/- 1.4 vs. 15.9 +/- 2.9%]. T had smaller fiber cross-sectional areas [3,413 +/- 677 (T) vs. 3,895 +/- 447 microns 2 (N); P < 0.05] but had similar number of capillaries per muscle fiber [1.35 +/- 0.23 (T) vs. 1.46 +/- 0.08 (N)] and muscle fiber area supplied per capillary [399 +/- 29 (T) vs. 382 +/- 65 mm2 (N)]. Total mitochondrial volume density was much lower in T (3.99 +/- 0.17%) than in N (5.51 +/- 0.19%) (P < 0.025). Mirroring mitochondrial volume density, citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities were lower in T than in N (P < 0.05). The activities of L-lactate dehydrogenase and hexokinase were the same in both groups. T had significantly less muscle fiber lipid droplets than did N, which correlated with the low activity of 3-hydroxyacyl-CoA dehydrogenase (r = 0.57, P = 0.02). In conclusion, lowland-born T have a low mitochondrial volume-to-specific peak O2 consumption ratio, which, based on previous measurements on altitude-born Sherpas (B. Kayser, H. Hoppeler, H. Claassen and P. Cerretelli. J. Appl. Physiol. 70: 1938-1942, 1991), appears to be an inborn feature.

Is fiber mitochondrial volume density a good indicator of muscle fatigability to isometric exercise?

1991 ◽  
Vol 70 (5) ◽  
pp. 2111-2119 ◽  
Author(s):  
S. E. Alway
Keyword(s):  
Fiber Type ◽  
Isometric Exercise ◽  
Volume Density ◽  
Voluntary Contraction ◽  
The Other ◽  
Triceps Surae ◽  
Type I ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
Sedentary Subjects

The relationship between the ratio of interfibrillar mitochondrial volume density (Vvmit) to myofibrillar volume density (Vvmyo) and isometric fatigue characteristics of the human triceps surae was determined in six bodybuilders, six endurance athletes, and six active controls before and after 16 wk of isometric training at 30 or 100% maximal voluntary contraction (MVC) in six sedentary subjects in a unilateral exercise model. Time to fatigue at 30% MVC was significantly less in sedentary subjects before training than in the other subject groups, but it was similar to the other groups posttraining. Stereological analyses of type I fibers indicated that Vvmit/Vvmyo was less in bodybuilders than in other subjects. Training at 30% MVC increased type I fiber Vvmit/Vvmyo of the soleus by 11% but did not affect the gastrocnemii. Training at 100% MVC did not alter Vvmit/Vvmyo in any muscle, nor was this ratio changed in type II fibers by either training program. Despite the morphological differences, both training protocols increased relative endurance, although greater fatigue resistance was seen after training at 30% MVC. Correlation analyses indicated that isometric endurance and improvements in muscle endurance by isometric exercise were not dependent on increasing interfibrillar Vvmit or Vvmit/Vvmyo in either fiber type.

scholarly journals 145 President Oral Presentation Pick: Prenatal stress increases skeletal muscle mitochondrial volume density and function in yearling Brahman calves

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 120-121
Author(s):  
Chloey P Guy ◽  
Catherine L Wellman ◽  
David G Riley ◽  
Charles R Long ◽  
Ron D Randel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Creatine Kinase ◽  
Muscle Damage ◽  
Prenatal Stress ◽  
Citrate Synthase ◽  
Volume Density ◽  
Assembly Factor ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
And Function

Abstract We previously determined that prenatal stress (PNS) differentially affected methylation of DNA from leukocytes of 28-d-old calves. Specifically, COX14 (cytochrome c oxidase (COX) assembly factor) and CKMT1B (mitochondrial creatine kinase U-type) were hypomethylated and COA5 (COX assembly factor 5), COX5A (COX subunit 5A), NRF1 (nuclear respiratory factor 1), and GSST1 (glutathione S-transferase theta-1) were hypermethylated in PNS compared to non-PNS calves (P ≤ 0.05). Our current objective was to test the hypothesis that PNS exhibit impaired mitochondrial function and greater oxidative stress than non-PNS calves. Blood and longissimus dorsi muscle samples were collected from yearling Brahman calves whose mothers were stressed by 2 h transportation at 60, 80, 100, 120, and 140 days of gestation (PNS; 8 bulls, 6 heifers) and non-PNS calves (4 bulls, 6 heifers). Serum was evaluated for the stress hormone, cortisol, and muscle damage marker, creatine kinase; muscle was analyzed for mitochondrial volume density and function by citrate synthase (CS) and COX activities, respectively, concentration of malondialdehyde, a lipid peroxidation marker, and activity of the antioxidant, superoxide dismutase (SOD). Data were analyzed using mixed linear models with treatment and sex as fixed effects. Serum cortisol was numerically higher in PNS than non-PNS calves but was not statistically different. Muscle CS and COX activities relative to protein were greater in PNS than non-PNS calves (P ≤ 0.03), but COX relative to CS activity was similar between groups. Activity of COX was greater in bulls than heifers (P = 0.03), but no other measure was affected by sex. All other measures were unaffected by PNS. Prenatal stress did not affect markers of muscle damage and oxidative stress in yearling Brahman calves at rest but mitochondrial volume density and function were greater in PNS calves. Acute stressors induce oxidative stress, so implications of differences in mitochondria in PNS calves following a stressor should be investigated.

241 Skeletal Muscle Mitochondrial Capacities Are Impacted by Breed and Temperament in Young Angus and Brahman Steers

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 127-127
Author(s):  
Chloey P Guy ◽  
Lauren T Wesolowski ◽  
Audrey L Earnhardt ◽  
Dustin Law ◽  
Don A Neuendorff ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fixed Effects ◽  
Linear Models ◽  
Citrate Synthase ◽  
Volume Density ◽  
Skeletal Muscle Mitochondria ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
Brahman Steers ◽  
The Impact

Abstract Temperament impacts skeletal muscle mitochondria in Brahman heifers, but this has not been investigated in steers or between cattle breeds. We hypothesized mitochondrial measures would be greater in Angus than Brahman, temperamental than calm steers, and the trapezius (TRAP) than the longissimus thoracis (LT) muscle. Samples from calm (n = 13 per breed), intermediate (n = 12 per breed), and temperamental (n=13 per breed) Angus and Brahman steers (mean±SD 10.0±0.8 mo) were evaluated for mitochondrial enzyme activities via colorimetry. Calm and temperamental LT samples were evaluated for oxidative phosphorylation (P) and electron transfer (E) capacities by high-resolution respirometry. Data were analyzed using linear models with fixed effects of breed, muscle, temperament, and all interactions. Brahman tended to have greater mitochondrial volume density (citrate synthase activity; CS) than Angus (P = 0.08), while intrinsic (relative to CS) mitochondrial function (cytochrome c oxidase activity) was greater in Angus than Brahman (P = 0.001) and greater in TRAP than LT (P = 0.008). Angus exhibited greater integrative (per mg tissue) and intrinsic P with complex I (PCI), P with complexes I+II (PCI+II), maximum noncoupled E, and E with complex II (ECII; P ≤ 0.04) and tended to have greater intrinsic leak (P = 0.1) than Brahman. Contribution of PCI to total E was greater in Angus than Brahman (P = 0.01), while contribution of ECII to total E was greater in Brahman than Angus (P = 0.05). A trend for the interaction of breed and temperament (P = 0.07) indicated calm Angus had the greatest intrinsic ECII (P ≤ 0.03) while intrinsic ECII was similar between temperamental Angus and calm and temperamental Brahman. Integrative PCI+II and ECII, and the contribution of PCI and PCI+II to overall E tended to be greater in temperamental than calm steers (P ≤ 0.09), while intrinsic ECII tended to be greater in calm than temperamental steers (P = 0.07). The impact of these mitochondrial differences on meat quality measures remains to be determined.

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