NYMC Faculty Publications

Overexpression of TNF-α in Mitochondrial Diseases Caused by Mutations in mtDNA: Evidence for Signaling Through its Receptors on Mitochondria

Author Type(s)

Faculty

Journal Title

Free Radical Biology & Medicine

First Page

108

Last Page

114

Document Type

Article

Publication Date

10-1-2013

Department

Pharmacology

Keywords

Biopsy, DNA, Mitochondrial, Female, Gene Expression, Humans, Male, Mitochondria, Mitochondrial Diseases, Mutation, Oxidative Phosphorylation, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Signal Transduction, Tumor Necrosis Factor-alpha

Disciplines

Medicine and Health Sciences

Abstract

Mitochondrial diseases (MDs) are heterogeneous disorders due to impaired respiratory chain function causing defective ATP production. Although the disruption of oxidative phosphorylation is central to the MD pathophysiology, other factors may contribute to these disorders. We investigated the expression and the cellular localization of TNF-α and its receptors, TNFR1 and TNFR2, in muscle biopsies from 15 patients with mitochondrial respiratory chain dysfunction. Our data unambiguously demonstrate that TNF-α is expressed in muscle fibers with abnormal focal accumulations of mitochondria, so-called ragged red fibers, and is delivered to mitochondria where both receptors are localized. Moreover TNF receptors are differentially regulated in patients' muscle in which the expression levels of TNFR1 mRNA are decreased and those of TNFR2 mRNA are increased compared with controls. These findings suggest for the first time that TNF-α could exert a direct effect on mitochondria via its receptors.

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