Loss of Parkin Results in Altered Muscle Stem Cell Differentiation during Regeneration

Esteca, Marcos Vinícius; Severino, Matheus Brandemarte; Silvestre, João Guilherme; Santos, Gustavo Palmeira Dos; Tamborlin, Letícia; Luchessi, Augusto Ducati; Moriscot, Anselmo Sigari; Gustafsson, Åsa B.; Baptista, Igor L.

doi:10.3390/ijms21218007

Cited by 18 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the importance of metabolic reprogramming, other mitochondrial processes are implicated in optimal SC function. For instance, competent mitophagy has been shown to be necessary for normal SC activity in a study that examined Parkin null mice (Esteca et al, 2020). Parkin is an E3 ubiquitin ligase that is essential for regulation of mitophagy.…”

Section: Satellite Cell Mitochondrial Function and Vitamin Dmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health

et al. 2021

View full text Add to dashboard Cite

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (ROS) production, augments antioxidant capacity, and prevents oxidative stress, a common antagonist in muscle damage. Additionally, VDR knockdown results in decreased mitochondrial oxidative capacity and ATP production, suggesting that vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration. Vitamin D regulation of mitochondrial health may also have implications for SC activity and self-renewal capacity, which could further affect muscle regeneration. However, the optimal timing, form and dose of vitamin D, as well as the mechanism by which vitamin D contributes to maintenance and restoration of muscle strength following injury, have not been determined. More research is needed to determine mechanistic action of 1,25(OH)D on mitochondria and SCs, as well as how this action manifests following muscle injury in vivo. Moreover, standardization in vitamin D sufficiency cut-points, time-course study of the efficacy of vitamin D administration, and comparison of multiple analogs of vitamin D are necessary to elucidate the potential of vitamin D as a significant contributor to muscle regeneration following injury. Here we will review the contribution of vitamin D to skeletal muscle regeneration following injury.

show abstract

Section: Satellite Cell Mitochondrial Function and Vitamin Dmentioning

confidence: 99%

“…Parkin knockout resulted in increased SC proliferation and impaired differentiation in mouse skeletal muscle following injury with cardiotoxin. These changes in SC activity were accompanied by delayed skeletal muscle fiber repair and smaller muscle fibers during regeneration (Esteca et al, 2020).…”

Section: Satellite Cell Mitochondrial Function and Vitamin Dmentioning

confidence: 99%

Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Thus, it is reasonable to speculate that Parkin reduction is not the only mechanism for MuRF‐1 expression during CS exposure and that other possibilities should be elucidated. Third, a recent paper showed that Parkin‐mediated mitophagy might play a role in regulating muscle stem cell differentiation 43 . The results of our experiment demonstrated that CSE (2%) exposure induced a significantly lower expression levels of myogenin, a key transcription factor for myotube differentiation, in myoblasts, which was further reduced in CSE‐treated Parkin KD myoblasts (data not shown).…”

Section: Discussionmentioning

confidence: 46%

“…Third, a recent paper showed that Parkin‐mediated mitophagy might play a role in regulating muscle stem cell differentiation. 43 The results of our experiment demonstrated that CSE (2%) exposure induced a significantly lower expression levels of myogenin, a key transcription factor for myotube differentiation, in myoblasts, which was further reduced in CSE‐treated Parkin KD myoblasts (data not shown). Hence, it is likely that not only increased degradation of muscle proteins but also reduced muscle regeneration may be involved in the development of COPD‐related sarcopenia associated with insufficient Parkin‐mediated mitophagy, which should be examined in future studies.…”

Section: Discussionmentioning

confidence: 67%

Involvement of Parkin‐mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease‐related sarcopenia

Ito

Hashimoto

Tanihata

et al. 2022

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Sarcopenia is characterized by the loss of skeletal muscle mass and strength and is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) exposure, a major cause for COPD, induces mitochondrial damage, which has been implicated in sarcopenia pathogenesis. The current study sought to examine the involvement of insufficient Parkin-mediated mitophagy, a mitochondrion-selective autophagy, in the mechanisms by which dysfunctional mitochondria accumulate with excessive reactive oxygen species (ROS) production in the development of COPD-related sarcopenia. Methods The involvement of Parkin-mediated mitophagy was examined using in vitro models of myotube formation, in vivo CS-exposure model using Parkin À/À mice, and human muscle samples from patients with COPD-related sarcopenia. Results Cigarette smoke extract (CSE) induced myotube atrophy with concomitant 30% reduction in Parkin expression levels (P < 0.05). Parkin-mediated mitophagy regulated myotube atrophy by modulating mitochondrial damage and mitochondrial ROS production. Increased mitochondrial ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 (MuRF-1)-mediated myosin heavy chain (MHC) degradation. Parkin À/À mice with prolonged CS exposure showed enhanced limb muscle atrophy with a 31.7% reduction in limb muscle weights (P < 0.01) and 2.3 times greater MuRF-1 expression (P < 0.01) compared with wild-type mice with concomitant accumulation of damaged mitochondria and oxidative modifications in 4HNE expression. Patients with COPD-related sarcopenia exhibited significantly reduced Parkin but increased MuRF-1 protein levels (35% lower and 2.5 times greater protein levels compared with control patients, P < 0.01 and P < 0.05, respectively) and damaged mitochondria accumulation demonstrated in muscles. Electric pulse stimulation-induced muscle contraction prevented CSE-induced MHC reduction by maintaining Parkin levels in myotubes. Conclusions Taken together, COPD-related sarcopenia can be attributed to insufficient Parkin-mediated mitophagy and increased mitochondrial ROS causing enhanced muscle atrophy through MuRF-1 activation, which may be at least partly preventable through optimal physical exercise.

show abstract

“…Mitochondrial function is critical for muscle repair after injury considering its role in modulating satellite cells activity [61], as demonstrated by reduced oxidative capacity in quiescent satellite cells [62]. Moreover, modulation of mitochondrial mitophagy seems to be necessary to satellite cell function, as demonstrated in mouse models knock-out for Parkin, an E3 ubiquitin ligase [63], that showed reduced differentiation of satellite cells and, consequently, poor muscle regeneration. These data confirm that mitophagy favors the increase and maintenance of the satellite cells pool.…”

Section: Vitamin D and Sport-related Muscle Injury: From Biology To Clinical Practicementioning

confidence: 99%

Muscle Regeneration and Function in Sports: A Focus on Vitamin D

et al. 2021

View full text Add to dashboard Cite

Muscle is one of the main targets for the biological effects of vitamin D. This hormone modulates several functions of skeletal muscles, from development to tissue repair after injury, through genomic and non-genomic mechanisms. Vitamin D deficiency and supplementation seem to significantly affect muscle strength in different populations, including athletes, although optimal serum 25(OH)D3 level for sport performance has not been defined so far. Additionally, vitamin D deficiency results in myopathy characterized by fast-twitch fiber atrophy, fatty infiltration, and fibrosis. However, less is known about regenerative effects of vitamin D supplementation after sport-related muscle injuries. Vitamin D receptor (VDR) is particularly expressed in the embryonic mesoderm during intrauterine life and in satellite cells at all stages of life for recovery of the skeletal muscle after injury. Vitamin D supplementation enhances muscle differentiation, growth, and regeneration by increasing the expression of myogenic factors in satellite cells. The objective of this narrative review is to describe the role of vitamin D in sport-related muscle injury and tissue regeneration.

show abstract

Loss of Parkin Results in Altered Muscle Stem Cell Differentiation during Regeneration

Cited by 18 publications

References 37 publications

Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health

Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health

Involvement of Parkin‐mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease‐related sarcopenia

Muscle Regeneration and Function in Sports: A Focus on Vitamin D

Contact Info

Product

Resources

About