The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass

Abstract

The dynamic coordination of processes controlling the quality of the mitochondrial network is crucial to maintain the function of mitochondria in skeletal muscle. Changes of mitochondrial proteolytic system, dynamics (fusion/fission), and mitophagy induce pathways that affect muscle mass and performance. When muscle mass is lost, the risk of disease onset and premature death is dramatically increased. For instance, poor quality of muscles correlates with the onset progression of several age-related disorders such as diabetes, obesity, cancer, and aging sarcopenia. To date, there are no drug therapies to reverse muscle loss, and exercise remains the best approach to improve mitochondrial health and to slow atrophy in several diseases. This review will describe the principal mechanisms that control mitochondrial quality and the pathways that link mitochondrial dysfunction to muscle mass regulation.

Dynamic Changes to the Skeletal Muscle Proteome and Ubiquitinome Induced by the E3 Ligase, ASB2β

“…A disruption in the normal balance between mitochondrial fission and fusion can lead to the activation of proteasomeand autophagy-mediated protein degradation and muscle atrophy [for recent review see (62)]. In this context, it is interesting to note that our 10-day proteomic analysis identified a significant ASB2β-induced decrease in the abundance of the mitochondrial fusion-promoting, Optic Atrophy Protein 1 (Opa1; Log 2 FC −0.140; supplemental Table S1) (63), potentially contributing to a shift in the balance toward mitochondrial fission.…”

The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia

“…Defective mitochondria cannot be cleared by cellular division due to the postmitotic nature of skeletal muscle. Thus, in muscle the preservation of the mitochondrial network integrity relies on the coordination of mitochondria quality control systems, which are activated, according to the degree of mitochondrial damage, ranging from a local repair to a dysfunctional organelle’s whole degradation [ 26 ]. Among the defensive strategies, continuous rounds of mitochondrial biogenesis and fusion are balanced by opposing processes of mitochondrial fission and mitophagy, the selective degradation of mitochondria via autophagy, to ensure the fusion of newly formed mitochondria into the mitochondrial network and the elimination the dysfunctional organelles, respectively.…”

“…Thus, the constant reshaping of mitochondria by fusion and fission referred as mitochondrial dynamics is critical to keeping under control mitochondrial quality and function ( Figure 1 ). A failure in any of these systems predisposes to skeletal muscle dysfunction and degeneration [ 26 ]. Accordingly, alterations in mitochondrial content, morphology, and function are closely associated with muscle loss in sarcopenia and several age-related pathological conditions [ 26 ].…”

“…The defective organelles are further sequestered into autophagic vesicles for their degradation in the lysosome via the activation of mitophagy pathways [ 80 ]. In mammals, the selectivity of mitophagy is controlled by PINK1, Parkin, prohibitin 2, FUNDC1, AMBRA1, BNIP3, and BNIP3L/NIX [ 26 ]. The fine-tuning of the autophagy and mitophagy fluxes is critical for muscle mass maintenance [ 26 ].…”

“…In mammals, the selectivity of mitophagy is controlled by PINK1, Parkin, prohibitin 2, FUNDC1, AMBRA1, BNIP3, and BNIP3L/NIX [ 26 ]. The fine-tuning of the autophagy and mitophagy fluxes is critical for muscle mass maintenance [ 26 ]. Both excessive [ 71 , 78 , 81 ] and reduced general autophagy and mitophagy [ 82 , 83 , 84 , 85 ] contribute to muscle atrophy and weakness.…”