Details

Autor(en) / Beteiligte

• Sparks, Lauren M
• Redman, Leanne M
• Conley, Kevin E
• Harper, Mary-Ellen
• Hodges, Andrew
• Eroshkin, Alexey
• Costford, Sheila R
• Gabriel, Meghan E
• Yi, Fanchao
• Shook, Cherie
• Cornnell, Heather H
• Ravussin, Eric
• Smith, Steven R

Titel

Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in Muscle of Healthy Individuals

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2016-12, Vol.101 (12), p.4994-5003

Ort / Verlag

United States: Endocrine Society

Erscheinungsjahr

2016

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Context: Reduced mitochondrial coupling (ATP/O2 [P/O]) is associated with sedentariness and insulin resistance. Interpreting the physiological relevance of P/O measured in vitro is challenging. Objective: To evaluate muscle mitochondrial function and associated transcriptional profiles in nonobese healthy individuals distinguished by their in vivo P/O. Design: Individuals from an ancillary study of Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy phase 2 were assessed at baseline. Setting: The study was performed at Pennington Biomedical Research Center. Participants: Forty-seven (18 males, 26–50 y of age) sedentary, healthy nonobese individuals were divided into 2 groups based on their in vivo P/O. Intervention: None. Main Outcome(s): Body composition by dual-energy x-ray absorptiometry, in vivo mitochondrial function (P/O and maximal ATP synthetic capacity) by 31P-magnetic resonance spectroscopy and optical spectroscopy were measured. A muscle biopsy was performed to measure fiber type, transcriptional profiling (microarray), and protein expressions. Results: No differences in body composition, peak aerobic capacity, type I fiber content, or mitochondrial DNA copy number were observed between the 2 groups. Compared with the uncoupled group (lower P/O), the coupled group (higher P/O) had higher rates of maximal ATP synthetic capacity (maximal ATP synthetic capacity, P < .01). Transcriptomics analyses revealed higher expressions of genes involved in mitochondrial remodeling and the oxidative stress response in the coupled group. A trend for higher mitonuclear protein imbalance (P = .06) and an elevated mitochondrial unfolded protein response (heat shock protein 60 protein; P = .004) were also identified in the coupled group. Conclusions: Higher muscle mitochondrial coupling is accompanied by an overall elevation in mitochondrial function, a novel transcriptional signature of oxidative stress and mitochondrial remodeling and indications of an mitochondrial unfolded protein response. Higher muscle mitochondrial coupling was accompanied by a novel transcriptional signature of oxidative stress and mitochondrial remodelling and an UPRmt, pointing toward a state of mitohormesis.