The Cellular Mitochondrial Genome Landscape in Disease

Anne Hahn; Steven Zuryn

doi:10.1016/j.tcb.2018.11.004

The Cellular Mitochondrial Genome Landscape in Disease

Trends Cell Biol. 2019 Mar;29(3):227-240. doi: 10.1016/j.tcb.2018.11.004. Epub 2018 Nov 30.

Authors

Anne Hahn¹, Steven Zuryn²

Affiliations

¹ The University of Queensland, Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research, Brisbane, Australia.
² The University of Queensland, Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research, Brisbane, Australia. Electronic address: s.zuryn@uq.edu.au.

PMID: 30509558
DOI: 10.1016/j.tcb.2018.11.004

Abstract

Mitochondrial genome (mitochondrial DNA, mtDNA) lesions that unbalance bioenergetic and oxidative outputs are an important cause of human disease. A major impediment in our understanding of the pathophysiology of mitochondrial disorders is the complexity with which mtDNA mutations are spatiotemporally distributed and managed within individual cells, tissues, and organs. Unlike the comparatively static nuclear genome, accumulating evidence highlights the variability, dynamism, and modifiability of the mtDNA nucleotide sequence between individual cells over time. In this review, we summarize and discuss the impact of mtDNA defects on disease within the context of a mosaic and shifting mutational landscape.

Keywords: ROS; aging; cancer; heteroplasmy; mitochondrial DNA (mtDNA); mitochondrial disease.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

DNA, Mitochondrial / genetics*
Genome, Mitochondrial / genetics*
Humans
Mitochondrial Diseases / genetics*
Mitochondrial Diseases / pathology
Mutation

Substances

DNA, Mitochondrial