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.

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.

• Authors: Ai-Hua Liu, Feng-Nan Niu, Lei-Lei Chang, Bing Zhang, Zhuo Liu, Jie-Yu Chen, Qiang Zhou, Hong-Yan Wu, Yun Xu
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 20 Issue 6 Pg. 509-14 (Jun 2014) ISSN: 1755-5949 [Electronic] England
• PMID: 24674659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Phosphorus Isotopes
• Electron Transport Complex IV

Topics

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