Cited by 24Muscle Physiology and DisordersAutophagy in Disease and TherapyMitochondrial Function and Pathology

Increased mitochondrial turnover in the skeletal muscle of fasted, castrated mice is related to the magnitude of autophagy activation and muscle atrophy

Rossetti, Michael L., Steiner, Jennifer L., Gordon, Bradley S.·2018·Molecular and Cellular Endocrinology

Abstract

Androgen-deficiency promotes muscle atrophy in part by increasing autophagy-mediated muscle protein breakdown during the fasted state, but factors contributing to this remain undefined. To identify novel factors, mice were subjected to sham or castration surgery. Seven-weeks post-surgery, mice were fasted overnight, refed for 30 min, and fasted another 4.5 h before sacrifice. BNIP3-mediated turnover of mitochondria was increased within the atrophied tibialis anterior (TA) of castrated mice and related to the magnitude of muscle atrophy and autophagy activation (i.e. decreased p62 protein content), thus linking turnover of potentially dysfunctional mitochondria with autophagy-mediated atrophy. Autophagy induction was likely facilitated by AMPK activation as a stress survival mechanism since phosphorylation of AMPK (Thr172), as well as the pro survival kinases Akt (Thr308) and (ERK1/2 Thr202/Tyr204), were increased by castration. Together, these data identify a novel relationship between mitochondrial turnover in the fasted state with autophagy activation and muscle atrophy following androgen depletion.

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Crossref · 10.1016/j.mce.2018.01.017

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  • Castration increases LC3 II/I ratio in the skeletal muscle of male mice, indicating that androgen deficiency increases mitophagy.

    “In addition, Castration increases LC3 II/I ratio in the skeletal muscle of male mice, indicating that androgen deficiency increases mitophagy (147, 148).”

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Authors
Rossetti, M. L., Steiner, J. L., & Gordon, B. S.
Affiliations
Florida State University (US)
Corresponding author
Gordon, Bradley S.
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2018-09
Volume
473
Pages
178-185
ISSN
0303-7207 (ISSN-L)
OpenAlex
W2793813106
Cited by
24
References
53
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 3 · 2019: 2 · 2018: 2
FWCI
1.25
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • DigiNole (Florida State University) (acceptedVersion)
Funders
  • Florida State University
  • University of Central Florida
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
mitochondrial turnover, skeletal muscle atrophy, autophagy, androgen deficiency, castration, fasting, BNIP3, p62, AMPK, Akt, ERK1/2, tibialis anterior, muscle protein degradation, mitochondrial dysfunction
MeSH terms
Sequestosome-1 Protein, Adenylate Kinase, Animals, Autophagy, Castration, Cell Survival, Fasting, Hydrogen Peroxide, Membrane Proteins, Mice, Inbred C57BL, Muscular Atrophy, Phenotype, Phosphorylation, Biomarkers, Muscle, Skeletal, Mitochondrial Proteins, Mitochondrial Turnover, Mitophagy

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