How does density of the inner mitochondrial membrane influence mitochondrial performance?

Heine, Kyle B.; Parry, Hailey A.; Hood, Wendy R.

doi:10.1152/ajpregu.00254.2022

Cited by 14 publications

(14 citation statements)

References 55 publications

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“…The mitochondrial membrane composition of fatty acids with high unsaturation that transport oxygen at high speed, fat droplet composition, and cytochrome oxidase expression levels are dynamically regulated. The present findings of mitochondrial observation by osmium-maceration SEM were consistent with these reports [32][33][34][35]. In addition, the establishment of a grading method to evaluate the length of cristae, mitochondria size, mitochondria-endoplasmic reticulum contact area, and mitochondria-lipid droplet contact area in a model of cardiac arrest organ damage caused by cold storage and cold perfusion can elucidate the mechanism of mitochondrial dysfunction described in this model and identify new therapeutic targets.…”

Section: Discussionsupporting

confidence: 91%

“…In the osmium-maceration SEM findings, differences in mitochondrial size and cristae, the mitochondrial inner membrane structure, were observed among the groups. The morphology of the mitochondrial inner membrane is important for the formation of proton gradients across the inner membrane for ATP synthesis, and increasing the density of the inner mitochondrial membrane alters the ATP production capacity of mitochondria [32,33]. External factors such as temperature also alter the mitochondrial size and area ratio of the inner and outer mitochondrial membranes [34], while internal factors such as lipid composition and unsaturation level alter energy production capacity [35].…”

Section: Discussionmentioning

confidence: 99%

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Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death

Sakamoto

Bochimoto

Shibata

et al. 2023

JCM

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Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation. The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H+]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7–10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death

Sakamoto

Bochimoto

Shibata

et al. 2023

JCM

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“…As posited by Heine et al. (2023), this could be because maintaining an effective electrochemical gradient, and by extension effective ATP production, becomes challenging if the mitochondrial cristae density becomes too high.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the absolute values for mitochondrial cristae density rarely exceed ∼40 μm 2 μm −3 , seemingly being an upper limit even in highly trained individuals. As posited by Heine et al (2023), this could be because maintaining an effective electrochemical gradient, and by extension effective ATP production, becomes challenging if the mitochondrial cristae density becomes too high.…”

Section: Effect Of Training Status On Oxphos and Intrinsic Mitochondr...mentioning

confidence: 99%

Skeletal muscle mitochondria demonstrate similar respiration per cristae surface area independent of training status and sex in healthy humans

Schytz,

Ørtenblad,

Lundby

et al. 2023

The Journal of Physiology

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The impact of training status and sex on intrinsic skeletal muscle mitochondrial respiratory capacity remains unclear. We examined this by analysing human skeletal muscle mitochondrial respiration relative to mitochondrial volume and cristae density across training statuses and sexes. Mitochondrial cristae density was estimated in skeletal muscle biopsies originating from previous independent studies. Participants included females (n = 12) and males (n = 41) across training statuses ranging from untrained (UT, n = 8), recreationally active (RA, n = 9), active‐to‐elite runners (RUN, n = 27) and cross‐country skiers (XC, n = 9). The XC and RUN groups demonstrated higher mitochondrial volume density than the RA and UT groups while all active groups (RA, RUN and XC) displayed higher mass‐specific capacity of oxidative phosphorylation (OXPHOS) and mitochondrial cristae density than UT. Differences in OXPHOS diminished between active groups and UT when normalising to mitochondrial volume density and were lost when normalising to muscle cristae surface area density. Moreover, active females (n = 6–9) and males (n = 15–18) did not differ in mitochondrial volume and cristae density, OXPHOS, or when normalising OXPHOS to mitochondrial volume density and muscle cristae surface area density. These findings demonstrate: (1) differences in OXPHOS between active and untrained individuals may be explained by both higher mitochondrial volume and cristae density in active individuals, with no difference in intrinsic mitochondrial respiratory capacity (OXPHOS per muscle cristae surface area density); and (2) no sex differences in mitochondrial volume and cristae density or mass‐specific and normalised OXPHOS. This highlights the importance of normalising OXPHOS to muscle cristae surface area density when studying skeletal muscle mitochondrial biology. imageKey points Oxidative phosphorylation is the mitochondrial process by which ATP is produced, governed by the electrochemical gradient across the inner mitochondrial membrane with infoldings named cristae. In human skeletal muscle, the mass‐specific capacity of oxidative phosphorylation (OXPHOS) can change independently of shifts in mitochondrial volume density, which may be attributed to variations in cristae density. We demonstrate that differences in skeletal muscle OXPHOS between healthy females and males, ranging from untrained to elite endurance athletes, are matched by differences in cristae density. This suggests that higher OXPHOS in skeletal muscles of active individuals is attributable to an increase in the density of cristae. These findings broaden our understanding of the variability in human skeletal muscle OXPHOS and highlight the significance of cristae, specific to mitochondrial respiration.

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“…Alterations in cristae morphology and matrix volume can provide equally important quantitative changes in BAT aging. Although there are morphological restraints, increased cristae volume generally correlates with an increased ATP potential [34] . Notably, inflammation of BAT has been demonstrated to cause loss of cristae structural integrity, possibly related to impaired UCP1 activation also observed [35] .…”

Section: Aged Bat Mitochondria Show Altered Cristae Volume Area and P...mentioning

confidence: 99%

Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue

Crabtree

Neikirk

Marshall

et al. 2023

Preprint

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Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content and abundance The physiological function and bioenergetic capacity of mitochondria are connected to the structure, folding, and organization of its inner-membrane cristae. During the aging process, mitochondrial dysfunction is observed, and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells. Therefore, we hypothesized that the morphological changes in BAT mitochondria and cristae observed across aging would reflect alterations to energy dynamics. We developed a quantitative three-dimensional (3D) electron microscopy approach to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, we investigated the 3D morphology of mitochondrial cristae in adult (3-month) and aged (2-year) murine BAT tissue via serial block face-scanning electron microscopy (SBF-SEM) and3D reconstruction software for manual segmentation, analysis, and quantification. Upon investigation, we found increases in mitochondrial volume, surface area, and complexity and decreased sphericity in aged BAT. Cristae examination revealed decreased cristae volume, perimeter, and complexity, with cristate appearing more heterogeneous. Overall, these data define the nature of the mitochondrial structure in BAT, showing loss of cristae definition across aging, suggesting alterations in functionality and bioactivity.

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How does density of the inner mitochondrial membrane influence mitochondrial performance?

Cited by 14 publications

References 55 publications

Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death

Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death

Skeletal muscle mitochondria demonstrate similar respiration per cristae surface area independent of training status and sex in healthy humans

Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue

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