Peroxisome Proliferator-activated Receptor γ Coactivator 1 (PGC-1)- and Estrogen-related Receptor (ERR)-induced Regulator in Muscle 1 (PERM1) Is a Tissue-specific Regulator of Oxidative Capacity in Skeletal Muscle Cells

Cho, Yoshitake; Hazen, Bethany C.; Russell, Aaron P.; Kralli, Anastasia

doi:10.1074/jbc.m113.489674

Cited by 92 publications

(116 citation statements)

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“…In previous studies, we found that Perm1 was required for the induction of mitochondrial biogenesis by PGC1a in cultured myotubes (32). Thus, we next assessed the effect of increased Perm1 expression on skeletal muscle mitochondrial content and oxidative activity.…”

Section: Resultsmentioning

confidence: 99%

“…Differentiated myotubes were infected on d 4 of differentiation with adenoviruses expressing LacZ (control) or Perm1 at multiplicity of infection 50 (32). Cells were harvested 24 h after infection.…”

Section: Cell Culturementioning

confidence: 99%

“…Besides skeletal and cardiac muscles, where its expression is very high, Perm1 is detectable only in brown adipose tissue, a depot that shares developmental and expression similarities to muscle (33). Skeletal muscle Perm1 levels are induced by endurance exercise and decreased in disease states with decreased oxidative capacity, as seen in patients with amyotrophic lateral sclerosis (32). Our findings suggested that the induction of Perm1 may be part of the mechanism by which exercise (and PGC-1/ERRs) regulates mitochondrial oxidative function in muscle.…”

mentioning

confidence: 99%

“…Our findings suggested that the induction of Perm1 may be part of the mechanism by which exercise (and PGC-1/ERRs) regulates mitochondrial oxidative function in muscle. Interestingly, Perm1 regulates the expression of only a subset of genes induced by PGC-1a or ERRg expression in C2C12 myotubes, suggesting that Perm1 selectively functions in specific PGC-1/ERR-driven pathways (32). The ability of Perm1 to control mitochondrial biogenesis or other PGC-1/ERR pathways in adult skeletal muscle is so far unknown.…”

mentioning

confidence: 99%

“…The extent to which muscle may have tissue-specific factors regulating mitochondrial biogenesis in response to exercise has not yet been addressed. In our previous study, we identified Perm1 (PPARGC1-and ESRRinduced regulator, muscle 1) as a protein with a remarkably muscle-specific expression, induced by PGC-1a and ERRa, and required for the enhancement of oxidative capacity by PGC-1a in cultured myotubes (32). Besides skeletal and cardiac muscles, where its expression is very high, Perm1 is detectable only in brown adipose tissue, a depot that shares developmental and expression similarities to muscle (33).…”

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Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

et al. 2015

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Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole‐body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age‐related muscle atrophy. Hence, elucidating the mechanisms that control muscle mitochondrial content and oxidative function can provide new insights into states and diseases that affect muscle health. In past studies, we identified Perm1 (PPARGC1‐ and ESRR‐induced regulator, muscle 1) as a gene induced by endurance exercise in skeletal muscle, and regulating mitochondrial oxidative function in cultured myotubes. The capacity of Perm1 to regulate muscle mitochondrial content and function in vivo is not yet known. In this study, we use adeno‐associated viral (AAV) vectors to increase Perm1 expression in skeletal muscles of 4‐wk‐old mice. Compared to control vector, AAV1‐Perm1 leads to significant increases in mitochondrial content and oxidative capacity (by 40‐80%). Moreover, AAV1‐Perm1‐transduced muscles show increased capillary density and resistance to fatigue (by 33 and 31 %, respectively), without prominent changes in fiber‐type composition. These findings suggest that Perm1 selectively regulates mitochondrial biogenesis and oxidative function, and implicate Perm1 in muscle adaptations that also occur in response to endurance exercise.—Cho, Y., Hazen, B. C., Gandra, P. G., Ward, S. R., Schenk, S., Russell, A. P., Kralli, A. Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle. FASEB J. 30, 674‐687 (2016). http://www.fasebj.org

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Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

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Estrogen‐Related Receptor Gamma (ERRγ) as Biomarker and Novel Target for Therapeutic Intervention on Cancer: A Review

Upadhyay,

Goel,

Gulwani

et al. 2024

Advanced Therapeutics

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Estrogen‐related receptors (ERRs), genes similar to estrogen receptors, are identified as hormone‐responsive systems associated with the ERR subfamily. These hormone‐responsive systems facilitate oncometabolic programs to nourish cancer cell growth, a central node at the interface of cellular energy metabolism and cancer. Several independent studies have implicated ERR isoforms like ERRα, ERRβ, and ERRγ in the pathways of cancer development and progression. The construction of tissue‐specific ERR transgenic or knockout mice and the application of synthetic ligands have precisely indicated the critical and diverse role of ERRγ than other isoforms. ERRγ, plays a critical and diverse role, enabling switching metabolism to oncometabolism in favor of cancer cells, making it a “hot target” in cancer therapy. ERRγ expression is correlated with the clinical status of diverse cancer types and various cancer tissue treatments. The dual feature of ERRγ raises interest in understanding its biogenesis and function in different tissues. This review aims to describe the structural organization of ERRs, their central occupancy at the interface of cancer and metabolism, and their biogenesis and expression profile across different cancers. It concludes that ERRγ has potential as a clinical marker in cancer prognosis and a novel non‐conventional therapeutic target.

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Skeletal Muscle Formation, Regeneration, and Recovery from Injury

Myers

2024

Skeletal Muscle Physiology

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Peroxisome Proliferator-activated Receptor γ Coactivator 1 (PGC-1)- and Estrogen-related Receptor (ERR)-induced Regulator in Muscle 1 (PERM1) Is a Tissue-specific Regulator of Oxidative Capacity in Skeletal Muscle Cells

Cited by 92 publications

References 70 publications

Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

Estrogen‐Related Receptor Gamma (ERRγ) as Biomarker and Novel Target for Therapeutic Intervention on Cancer: A Review

Skeletal Muscle Formation, Regeneration, and Recovery from Injury

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