Mitochondrial Complex Abundance, Mitophagy Proteins, and Physical Performance in People With and Without Peripheral Artery Disease

Anna Picca, Stephanie E. Wohlgemuth, Mary M. McDermott, Sunil K. Saini, Sudarshan Dayanidhi, Dongxue Zhang, Shujun Xu, Kate Kosmac, Lu Tian, Luigi Ferrucci, Robert L. Sufit, Emanuele Marzetti, Christiaan Leeuwenburgh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


BACKGROUND: Mitochondrial abnormalities exist in gastrocnemius muscle of people with peripheral artery disease (PAD). Whether abnormalities in mitochondrial biogenesis and autophagy are associated with greater ischemia or walking impairment in PAD is unknown. METHODS AND RESULTS: Protein markers of mitochondrial biogenesis and autophagy and the abundance of mitochondrial electron transport chain complexes were quantified in gastrocnemius muscle biopsies from people with and without PAD. Their 6-minute walk distance and 4-m gait speed were measured. Sixty-seven participants (mean age 65.0 years [±6.8], 16 [23.9%] women, 48 [71.6%] Black) were enrolled, including 15 with moderate to severe PAD (ankle brachial index [ABI] <0.60), 29 with mild PAD (ABI 0.60–0.90), and 23 without PAD (ABI 1.00–1.40). Abundance of all electron transport chain complexes was significantly higher in participants with lower ABI (eg, complex I: 0.66, 0.45, 0.48 arbitrary units [AU], respectively, P trend=0.043). Lower ABI values were associated with a higher LC3A/B II-to-LC3A/B I (microtubule-associated protein 1A/1B-light chain 3) ratio (2.54, 2.31, 2.15 AU, respectively, P trend=0.017) and reduced abundance of the autophagy receptor p62 (0.71, 0.69, 0.80 AU, respectively, P trend=0.033). The abundance of each electron transport chain complex was positively and significantly associated with 6-minute walk distance and 4-m gait speed at usual and fast pace only among participants without PAD (eg, complex I: r=0.541, P=0.008; r=0.477, P=0.021; r=0.628, P=0.001, respectively). CONCLUSIONS: These results suggest that accumulation of electron transport chain complexes in gastrocnemius muscle of people with PAD may be because of impaired mitophagy in the setting of ischemia. Findings are descriptive, and further study in larger sample sizes is needed.

Original languageEnglish (US)
Article numbere027088
JournalJournal of the American Heart Association
Issue number6
StatePublished - Mar 21 2023


  • ankle-brachial index
  • electron transport chain
  • mitochondrial biogenesis
  • mtDNA damage
  • muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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