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Am J Physiol Endocrinol Metab. 2019 Feb 1;316(2):E268-E285. doi: 10.1152/ajpendo.00314.2018. Epub 2019 Jan 2.

Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis.

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Division of Exercise Physiology, West Virginia University School of Medicine , Morgantown, West Virginia.
Mitochondria, Metabolism, and Bioenergetics Working Group, West Virginia University School of Medicine , Morgantown, West Virginia.
West Virginia University School of Pharmacy , Morgantown, West Virginia.
Toxicology Working Group, West Virginia University School of Medicine , Morgantown, West Virginia.


Type 2 diabetes mellitus (T2DM) is a systemic disease characterized by hyperglycemia, hyperlipidemia, and organismic insulin resistance. This pathological shift in both circulating fuel levels and energy substrate utilization by central and peripheral tissues contributes to mitochondrial dysfunction across organ systems. The mitochondrion lies at the intersection of critical cellular pathways such as energy substrate metabolism, reactive oxygen species (ROS) generation, and apoptosis. It is the disequilibrium of these processes in T2DM that results in downstream deficits in vital functions, including hepatocyte metabolism, cardiac output, skeletal muscle contraction, β-cell insulin production, and neuronal health. Although mitochondria are known to be susceptible to a variety of genetic and environmental insults, the accumulation of mitochondrial DNA (mtDNA) mutations and mtDNA copy number depletion is helping to explain the prevalence of mitochondrial-related diseases such as T2DM. Recent work has uncovered novel mitochondrial biology implicated in disease progressions such as mtDNA heteroplasmy, noncoding RNA (ncRNA), epigenetic modification of the mitochondrial genome, and epitranscriptomic regulation of the mtDNA-encoded mitochondrial transcriptome. The goal of this review is to highlight mitochondrial dysfunction observed throughout major organ systems in the context of T2DM and to present new ideas for future research directions based on novel experimental and technological innovations in mitochondrial biology. Finally, the field of mitochondria-targeted therapeutics is discussed, with an emphasis on novel therapeutic strategies to restore mitochondrial homeostasis in the setting of T2DM.


diabetes mellitus; mitochondria dysfunction

[Available on 2020-02-01]
[Indexed for MEDLINE]

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