High cytochrome c oxidase expression links to severe skeletal energy failure by 31P-MRS spectroscopy in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

Abstract

Aims: The purpose of this study was to evaluate the energy metabolism and mitochondrial function in skeletal muscle from patients with Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) or chronic progressive external ophthalmoplegia (CPEO) using phosphorus magnetic resonance spectroscopy (31P-MRS), to determine whether abnormally increasing cytochrome c oxidase (COX), as detected in muscle biopsy, could be a cause for MELAS. Methods: 31P-MRS was performed on the quadriceps femoris muscle of 12 healthy volunteers and 11 patients diagnosed as MELAS or CPEO by muscle biopsy and genetic analysis. All subjects experienced a state of rest, 5-min exercise, and 5-min recovery protocol in a supine position. Results: Compared to CPEO, MELAS patients typically exhibited COX-positive ragged-red fibers (RRFs) as well as strongly SDH-positive blood vessels (SSVs). However, based on 31P-MRS results, MELAS showed a higher inorganic phosphate (Pi)/phosphocreatine (PCr) ratio and lower ATP/PCr ratio during exercise and delayed Pi/PCr and ATP/PCr recovery to normal. Conclusions: This study suggests that high COX expression contributes to severe skeletal energy failure by 31P-MRS spectroscopy in MELAS. © 2014 John Wiley & Sons Ltd.