RGD Reference Report - Effect of denervation-induced muscle disuse on mitochondrial protein import. - Rat Genome Database

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Effect of denervation-induced muscle disuse on mitochondrial protein import.

Authors: Singh, Kaustabh  Hood, David A 
Citation: Singh K and Hood DA, Am J Physiol Cell Physiol. 2011 Jan;300(1):C138-45. doi: 10.1152/ajpcell.00181.2010. Epub 2010 Oct 13.
RGD ID: 13463487
Pubmed: PMID:20943961   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpcell.00181.2010   (Journal Full-text)

This study determined whether muscle disuse affects mitochondrial protein import and whether changes in protein import are related to mitochondrial content and function. Protein import was measured using a model of unilateral peroneal nerve denervation in rats for 3 (n = 10), 7 (n = 12), or 14 (n = 14) days. We compared the import of preproteins into the matrix of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria isolated from the denervated and the contralateral control tibialis anterior muscles. Denervation led to 50% and 29% reductions in protein import after 14 days of disuse in SS and IMF mitochondria, respectively. This was accompanied by significant decreases in mitochondrial state 3 respiration, muscle mass, and whole muscle cytochrome c oxidase activity. To investigate the mechanisms involved, we assessed disuse-related changes in 1) protein import machinery components and 2) mitochondrial function, reflected by respiration and reactive oxygen species (ROS) production. Denervation significantly reduced the expression of translocases localized in the inner membrane (Tim23), outer membrane (Tom20), and mitochondrial heat shock protein 70 (mtHsp70), especially in the SS subfraction. Denervation also resulted in elevated ROS generation, and exogenous ROS was found to markedly reduce protein import. Thus our data indicate that protein import kinetics are closely related to alterations in mitochondrial respiratory capacity (r = 0.95) and are negatively impacted by ROS. Deleterious changes in the protein import system likely facilitate the reduction in mitochondrial content and the increase in organelle dysfunction (i.e., increased ROS production and decreased respiration) during chronic disuse, which likely contribute to the activation of degradative pathways leading to muscle atrophy.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Timm23  (translocase of inner mitochondrial membrane 23)
Tomm20  (translocase of outer mitochondrial membrane 20)

Genes (Mus musculus)
Timm23  (translocase of inner mitochondrial membrane 23)
Tomm20  (translocase of outer mitochondrial membrane 20)

Genes (Homo sapiens)
TIMM23  (translocase of inner mitochondrial membrane 23)
TOMM20  (translocase of outer mitochondrial membrane 20)


Additional Information