Subcellular origin of mitochondrial DNA deletions in human skeletal muscle.

ABSTRACT:

Objective

In patients with mitochondrial DNA (mtDNA) maintenance disorders and with aging, mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to identify the sub-cellular origin and potential mechanisms underlying this process.

Methods

Serial skeletal muscle cryosections from patients with multiple mtDNA deletions were subjected to subcellular immunofluorescent, histochemical, and genetic analysis.

Results

We report respiratory chain-deficient perinuclear foci containing mtDNA deletions, which show local elevations of both mitochondrial mass and mtDNA copy number. These subcellular foci of respiratory chain deficiency are associated with a local increase in mitochondrial biogene

SUBMITTER: Vincent AE 

PROVIDER: S-EPMC6141001 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature