Low abundance of Mfn2 protein correlates with reduced mitochondria‐SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images

Castro-Sepúlveda, Mauricio; Fernández‐Verdejo, Rodrigo; Tuñón-Suárez, Mauro; Morales-Zúñiga, Jorge; Troncoso, Mayarling Francisca; Jannas-Vela, Sebastián; Zbinden‐Foncea, Hermann

doi:10.1096/fj.202002615rr

Cited by 16 publications

(20 citation statements)

References 39 publications

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“…Once again, similar observations were previously made in the liver, as the postprandial state was associated with reduced mitochondria cristae length through a Mfn2 and Opa1‐dependent mechanism 11 . Finally, we recently showed that a low Mfn2 protein abundance correlates with reduced mitochondria‐SR interactions and mitochondrial cristae density in human skeletal muscle 33 . Our results indicate that the fasting‐feeding transition‐induces mitochondrial dynamics modifications was not accompanied by changes in mitochondrial density as measured by Transmission electron microscopy and mitochondrial complexes density.…”

Section: Discussionsupporting

confidence: 84%

“…11 Finally, we recently showed that a low Mfn2 protein abundance correlates with reduced mitochondria-SR interactions and mitochondrial cristae density in human skeletal muscle. 33 Our results indicate that the fasting-feeding transition-induces mitochondrial dynamics modifications was not accompanied by changes in mitochondrial density as measured by Transmission electron microscopy and mitochondrial complexes density. The exception was the mitochondrial CV-ATP5A, which decreased after glucose load.…”

Section: Discussionmentioning

confidence: 51%

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The fasting‐feeding metabolic transition regulates mitochondrial dynamics

et al. 2021

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In humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75-g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate-treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R-mediated mitochondrial Ca 2+ accumulation. This allowed us to evaluate the role of ER-mitochondria Ca 2+ exchange in the mitochondrial dynamic response to substrate availability.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 51%

The fasting‐feeding metabolic transition regulates mitochondrial dynamics

et al. 2021

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“…Therefore, none of these proteins appear to play a role in the severity of COVID-19. Future studies should measure other proteins that also regulate mitochondrial cristae density, such as MICOS complex like MIC60 (Castro-Sepulveda et al, 2021;Yang et al, 2015). During hospitalization, patients with well-controlled glycemia show lower mortality than patients with poorly controlled glycemia (upper limit of glycemic variability exceeding 10.0 mmol/L) (Zhu et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Sections of 80‐nm were cut, mounted on electron microscopy grids, and examined using a transmission electron microscope (Philips, Tecnai 12 at 80 kV). Mitochondrial density was evaluated as previously described (Castro‐Sepulveda et al, 2021; Castro‐Sepúlveda et al, 2021; Echeverria et al, 2021). Mitochondrial density (%) and size (μm 2 ) were assessed in 4–6 cells per subject, and 3–10 mitochondria per cells.…”

Section: Methodsmentioning

confidence: 99%

“…Perturbations in mitochondrial dynamics, including mitochondrial size (mitochondrial fusion) and density, as well as mitochondrial cristae density, could also be involved. Indeed, perturbed mitochondrial dynamics (fusion/fission) are a feature of populations at high risk of severe COVID‐19, including the elderly (Sebastián et al, 2016), subjects with type 2 diabetes (Kelley et al, 2002), and subjects with low cardiorespiratory fitness (Castro‐Sepulveda et al, 2020; Castro‐Sepulveda et al, 2021; Nielsen et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Severe COVID‐19 correlates with lower mitochondrial cristae density in PBMCs and greater sitting time in humans

Castro-Sepúlveda

Tapia

Tuñón-Suárez

et al. 2022

Physiological Reports

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An interaction between mitochondrial dynamics, physical activity levels, and COVID‐19 severity has been previously hypothesized. However, this has not been tested. We aimed to compare mitochondrial morphology and cristae density of PBMCs between subjects with non‐severe COVID‐19, subjects with severe COVID‐19, and healthy controls. Additionally, we compared the level of moderate‐vigorous physical activity (MVPA) and sitting time between groups. Blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images and western blot of protein that regulate mitochondrial dynamics. The International Physical Activity Questionnaire (IPAQ; short version) was used to estimate the level of MVPA and the sitting time The patients who develop severe COVID‐19 (COVID‐19++) not present alterations of mitochondrial size neither mitochondrial density in comparison to non‐severe patients COVID‐19 (COVID‐19) and control subjects (CTRL). However, compared to CTRL, COVID‐19 and COVID‐19++ groups have lower mitochondrial cristae length, a higher proportion of abnormal mitochondrial cristae. The COVID‐19++ group has lower number (trend) and length of mitochondrial cristae in comparison to COVID‐19 group. COVID‐19, but not COVID‐19++ group had lower Opa 1, Mfn 2 and SDHB (Complex II) proteins than CTRL group. Besides, COVID‐19++ group has a higher time sitting. Our results show that low mitochondrial cristae density, potentially due to physical inactivity, is associated with COVID‐19 severity.

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Characterization of differential distribution patterns between mitofusin isoforms and their interaction in developing skeletal muscles of rat

Senapati,

Pani,

Rout

et al. 2023

J of Cellular Biochemistry

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Skeletal muscle during postnatal development undergoes several structural and biochemical modifications. It is proposed that these changes are closely intertwined with the increase in load‐bearing capacity of the muscle (i.e., myofibrils) and molecular machinery to support the energy demand (i.e., mitochondria). Concomitant establishment of the sarcoplasmic reticulum (SR) and mitochondrial network seems to be a major developmental adjustment of skeletal muscle leading to adult phenotype. Here, we have studied oxidativeness, vascularization, and the changes in mitofusins (Mfn) 1–Mfn 2 expression and interaction in the due course of muscle development. Toward this, we used a series of histochemical techniques to compare neonatal and adult limb muscles (Gastrocnemius and Quadriceps) of Wistar rat (Rattus norvegicus). Additionally, we probed the proximity between Mfn 1 and Mfn 2 using a highly sensitive antibody‐based proximity ligation assay indicating the change in mitochondrial fusion pattern or mitochondria‐SR interaction. The results show that neonatal fibers bear a uniform distribution of mitochondria while a differential pattern of distribution is seen in adults. The distribution of the blood vessels is also quite distinct in adult muscles with a well‐formed capillary network but in neonates, only central blood vessels are seen. Interestingly, our Mfn 1–Mfn 2 interaction data show that this interaction is uniformly distributed throughout the neonatal fibers, while it becomes peripherally localized in fibers of adult muscles. This peripheralization of Mfn 1–Mfn 2 interaction must be an important event of muscle development and might be critical to cater to the metabolic needs of adult muscle.

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Low abundance of Mfn2 protein correlates with reduced mitochondria‐SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images

Cited by 16 publications

References 39 publications

The fasting‐feeding metabolic transition regulates mitochondrial dynamics

The fasting‐feeding metabolic transition regulates mitochondrial dynamics

Severe COVID‐19 correlates with lower mitochondrial cristae density in PBMCs and greater sitting time in humans

Characterization of differential distribution patterns between mitofusin isoforms and their interaction in developing skeletal muscles of rat

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