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

CNS Neurosci Ther. 2014 Jun;20(6):509-14. doi: 10.1111/cns.12257. Epub 2014 Mar 27.

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 ((31)P-MRS), to determine whether abnormally increasing cytochrome c oxidase (COX), as detected in muscle biopsy, could be a cause for MELAS.

Methods: (31)P-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 (31)P-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 (31)P-MRS spectroscopy in MELAS.

Keywords: 31P-MRS; Cytochrome c oxidase; Energy metabolism; Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; Muscle biopsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Case-Control Studies
  • Electron Transport Complex IV / metabolism*
  • Female
  • Humans
  • Isometric Contraction / physiology
  • MELAS Syndrome / genetics
  • MELAS Syndrome / pathology*
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Ophthalmoplegia, Chronic Progressive External / genetics
  • Ophthalmoplegia, Chronic Progressive External / pathology
  • Phosphorus Isotopes
  • Young Adult

Substances

  • Phosphorus Isotopes
  • Electron Transport Complex IV