What is the role of mitochondrial abnormalities in the pathophysiology of sporadic inclusion body myositis (s-IBM)?

Updated: Jun 08, 2018
  • Author: Michael P Collins, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

As a likely secondary phenomenon, various mitochondrial abnormalities have been identified in s-IBM muscle, including ragged red fibers, cytochrome c oxidase-deficient fibers, and multiple mitochondrial DNA (mtDNA) mutations. [51, 52, 53] These changes might be mediated by aberrant mtDNA replication and maintenance due to oxidative stress, abnormal APP overexpression, [54] or proinflammatory cytokines. [55]

The downstream pathologic effects of the degenerative process were investigated in a recent proteomic, histochemical, and immunohistochemical study, which demonstrated preferential type 2 (fast twitch) myofiber involvement in most s-IBM muscles. [56] In particular, many fast twitch-specific structural proteins were differentially reduced. Expression of the corresponding gene transcripts was relatively preserved, suggesting that the protein loss was not caused by transcriptional failure. Four glycolytic enzymes were also decreased, especially glycogen-debranching enzyme.


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