Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers

Burke, Sarah; Solania, Angelo; Wolan, Dennis W.; Cohen, Michael S.; Ryan, Terence E.; Hepple, Russell T.

doi:10.3390/cells10102586

Cited by 12 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with a previous study where they also reported a significantly higher level of SIRT3 and SOD2 in the skeletal muscle of master athletes (~15 years younger than studied here) compared to age-matched controls ( Koltai et al, 2018 ). Finally, mitochondrial permeability transition is an important source of elevated mitochondrial ROS in skeletal muscle ( Burke et al, 2021 ) and SIRT3, which was elevated in MA, reduces mitochondrial permeability transition by deacetylation of cyclophilin D ( Hafner et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians

Ubaida‐Mohien

Spendiff

Lyashkov

et al. 2022

eLife

View full text Add to dashboard Cite

Background: Master athletes prove that preserving a high level of physical function up to very late in life is possible, but the mechanisms responsible for their high function remain unclear. Methods: We performed muscle biopsies in 15 octogenarian world class track and field masters athletes (MA) and 14 non-athlete age/sex-matched controls (NA) to provide insights into mechanisms for preserving function in advanced age. Muscle samples were assessed for respiratory compromised fibers, mtDNA copy number, and proteomics by liquid-chromatography mass spectrometry. Results: MA exhibited markedly better performance on clinical function tests and greater cross-sectional area of the vastus lateralis muscle. Proteomics analysis revealed marked differences, where most of the ~800 differentially represented proteins in MA versus NA pertained to mitochondria structure/function such as electron transport capacity (ETC), cristae formation, mitochondrial biogenesis, and mtDNA-encoded proteins. In contrast, proteins from the spliceosome complex and nuclear pore were downregulated in MA. Consistent with proteomics data, MA had fewer respiratory compromised fibers, higher mtDNA copy number, and an increased protein ratio of the cristae-bound ETC subunits relative to the outer mitochondrial membrane protein voltage dependent anion channel. There was a substantial overlap of proteins overrepresented in MA versus NA with proteins that decline with aging and which are higher in physically active than sedentary individuals. However, we also found 176 proteins related to mitochondria that are uniquely differentially expressed in MA. Conclusions: We conclude that high function in advanced age is associated with preserving mitochondrial structure/function proteins, with under-representation of proteins involved in the spliceosome and nuclear pore complex. Whereas many of these differences in MA appear related to their physical activity habits, others may reflect unique biological (e.g., gene, environment) mechanisms that preserve muscle integrity and function with aging. Funding: Funding for this study was provided by operating grants from the Canadian Institutes of Health Research (MOP 84408 to TT and MOP 125986 to RTH). Supported in part by the Intramural Research Program of the National Institute on Aging, NIH, Baltimore, MD, United States.

show abstract

Section: Discussionmentioning

confidence: 99%

Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians

Ubaida‐Mohien

Spendiff

Lyashkov

et al. 2022

eLife

View full text Add to dashboard Cite

show abstract

“…Sporadic denervation in mouse muscle has been shown to reduce mitochondrial respiratory capacity and increase sensitivity to mPTP opening [ 172 ]. Furthermore, mitochondrial permeability shift has been identified as a new pathogenesis of skeletal muscle atrophy, which acts through mitochondrial ROS emission and Caspase-3 activation [ 173 ]. It is worth noting that the mPTP activation is associated with mitochondrial Ca 2+ homeostasis and mitochondrial ROS, which together influence mitochondrial function.…”

Section: Role Of Mitochondria In Muscle Atrophymentioning

confidence: 99%

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Chen¹,

Ji²,

Liu³

et al. 2023

J Transl Med

View full text Add to dashboard Cite

Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.

show abstract

“…It has been demonstrated that mPTP induction activates caspase‐3 activity in myofiber atrophy. 28 Caspase‐3 activity was blocked in liver‐specific CypD knockout mice in the I/R model, as indicated by cleaved caspase‐3 expression. Therefore, CypD may contribute to hepatocyte apoptosis in a caspase‐3‐dependent manner in liver I/R injury.…”

Section: Discussionmentioning

confidence: 98%

“…The activation and function of caspases, which are involved in the delicate caspase–cascade system, is vital in the process of apoptotic signal conduction. It has been demonstrated that mPTP induction activates caspase‐3 activity in myofiber atrophy 28 . Caspase‐3 activity was blocked in liver‐specific CypD knockout mice in the I/R model, as indicated by cleaved caspase‐3 expression.…”

Section: Discussionmentioning

confidence: 99%

Cyclophilin D as a potential therapeutic target of liver ischemia/reperfusion injury by mediating crosstalk between apoptosis and autophagy

Yang

Wang

Xie³

et al. 2023

Chronic Diseases and Translational Medicine

View full text Add to dashboard Cite

BackgroundLiver ischemia/reperfusion (I/R) injury is a complex and multifactorial pathophysiological process. It is well recognized that the membrane permeability transition pore (mPTP) opening of mitochondria plays a crucial role in cell death after I/R injury. Cyclophilin D (CypD) is a critical positive regulator of mPTP. However, the effect of CypD on the pathogenesis of liver I/R injury and whether CypD is a potential therapeutic target are still unclear.MethodsWe constructed liver‐specific CypD knockout and AAV8‐peptidyl prolyl isomerase F (PPIF) overexpression mice. Then, a 70% liver I/R injury model was established in mice, with 90 min of ischemia and 6 h of reperfusion. The liver function was detected by the level of serum glutamic pyruvic transaminase (alanine transaminase) and glutamic oxaloacetic transaminase (aspartate aminotransferase), the liver damage score and degree of necrosis were measured by hematoxylin and eosin (H&E) staining of liver tissues. Reactive oxygen species (ROS) staining, apoptosis, and autophagy‐related molecules were used to detect apoptosis and autophagy during liver I/R.ResultsThe liver‐specific knockout of CypD alleviated necrosis and dysfunction in liver I/R injury, by reducing the excessive production of ROS, and inhibiting cell apoptosis and autophagy. On the contrary, overexpression of CypD exacerbated I/R‐induced liver damage.ConclusionWe found that the downregulation of CypD expression alleviated liver I/R injury by reducing apoptosis and autophagy through caspase‐3/Beclin1 crosstalk; in contrast, the upregulation of CypD expression aggravated liver I/R injury. Therefore, interfering with the expression of CypD seems to be a promising treatment for liver I/R injury.

show abstract

Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers

Cited by 12 publications

References 42 publications

Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians

Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Cyclophilin D as a potential therapeutic target of liver ischemia/reperfusion injury by mediating crosstalk between apoptosis and autophagy

Contact Info

Product

Resources

About