High Cytochrome c Oxidase Expression Links to Severe Skeletal Energy Failure by 31 P‐ MRS Spectroscopy in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke‐Like Episodes

摘要

Summary 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 ( RRF s) as well as strongly SDH ‐positive blood vessels ( SSV s). However, based on 31P‐ MRS results, MELAS showed a higher inorganic phosphate (Pi)/phosphocreatine ( PC r) ratio and lower ATP / PC r ratio during exercise and delayed Pi/ PC r and ATP / PC r recovery to normal. Conclusions This study suggests that high COX expression contributes to severe skeletal energy failure by 31P‐ MRS spectroscopy in MELAS .