Mitochondrial dysfunction and role of harakiri in the pathogenesis of myositis.

A new interesting article has been published in J Pathol. 2019 May 28. doi: 10.1002/path.5309. and titled:

Mitochondrial dysfunction and role of harakiri in the pathogenesis of myositis.

Authors of this article are:

Boehler JF, Horn A, Novak J, Li N, Ghimbovschi S, Lundberg IE, Alexanderson H, Munters LA, Jaiswal JK, Nagaraju K.

A summary of the article is shown below:

The etiology of myositis is unknown. Although attempts to identify viruses in myositis skeletal muscle have failed, several studies have identified the presence of a viral signature in myositis patients. Here we postulate that in individuals with susceptible genetic backgrounds, viral infection alters the epigenome to activate the pathological pathways leading to disease onset. To identify epigenetic changes, methylation profiling of Coxsackie B infected human myotubes and muscle biopsies from polymyositis (PM) and dermatomyositis (DM) patients were compared to changes in global transcript expression induced by in vitro Coxsackie B infection. Gene and protein expression analysis and live cell imaging were performed to examine the mechanisms. Analysis of methylation and gene expression changes identified that a mitochondria-localized activator of apoptosis – harakiri (HRK) – is up-regulated in myositis skeletal muscle cells. Muscle cells with higher HRK expression have reduced mitochondrial potential and poor ability to repair from injury as compared to controls. In cells from myositis patient Toll-like receptor 7 (TLR7) activates and sustains high HRK expression. Forced over expression of HRK in healthy muscle cells is sufficient to compromise their membrane repair ability. Moderate training exercise that is associated with improved muscle and mitochondrial function in PM and DM patients decreased TLR7 and HRK expression identifying these as therapeutic targets. Increased HRK and TLR7 expression causes mitochondrial damage leading to poor myofiber repair, myofiber death and muscle weakness in myositis patients and exercise induced reduction of HRK and TLR7 expression in patients is associated with disease amelioration. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.

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