We showed that
humanin (HN), an endogenous
peptide against
Alzheimer disease-related insults, was expressed in muscles of patients with
chronic progressive external ophthalmoplegia (
CPEO), a major
mitochondrial disease. Because HN was recently found to block proapoptotic Bax function and exert its versatile cytoprotective effects in association with an increase in
ATP levels, HN expression may thus reflect a physiological response against degenerative changes in the muscles of patients with
CPEO. We found HN expression in all four patients examined, each of whom had different
mitochondrial DNA mutations including two different single
DNA deletions, multiple deletions, and no major mutations detected. We also found that HN expression was not linked to focal
cytochrome c deficiency, strongly associated with the subtype of
CPEO with single deletions. These results suggest that HN expression is more closely related to degenerative changes in all types of
CPEO. Notably, HN was also expressed in non-degenerative muscle fibers of patients with
CPEO or
Leigh syndrome, who had the 8993T>G mutation in the mitochondrial
ATPase 6 gene known to be associated with impaired
ATP synthesis. Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities.