Mouse models of mitochondrial complex I dysfunction

• Published in: The international journal of biochemistry & cell biology 2013-01, Vol.45 (1), p.34-40
• Main Authors: Irwin, Michael H., Parameshwaran, Kodeeswaran, Pinkert, Carl A.
• Format: Article
• Language: English
• Subjects: animal models; Animals; cardiomyopathy; chemical compounds; Complex I; Disease Models, Animal; DNA, Mitochondrial - metabolism; Electron Transport Complex I - metabolism; energy; energy requirements; Gene Targeting; genes; Humans; Mice; Mitochondria; Mitochondria - metabolism; Mitochondrial Diseases - metabolism; Mouse model; muscular diseases; mutation; myocytes; neurons; Oxidative Phosphorylation; protein subunits; skeletal muscle; therapeutics
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2012.08.009

Diseases of the mitochondria generally affect cells with high-energy demand, and appear to most profoundly affect excitatory cells that have localized high energy requirements, such as neurons and cardiac and skeletal muscle cells. Complex I of the mammalian mitochondrial respiratory chain is a very large, 45 subunit enzyme, and functional deficiency of complex I is the most frequently observed cause of oxidative phosphorylation (OXPHOS) disorders. Impairment of complex I results in decreased cellular energy production and is responsible for a variety of human encephalopathies, myopathies and cardiomyopathies. Complex I deficiency may be caused by mutations in any of the seven mitochondrial or 38 nuclear genes that encode complex I subunits or by mutations in various other nuclear genes that affect complex I assembly or function. Mouse models that faithfully mimic human complex I disorders are needed to better understand the role of complex I in health and disease and for evaluation of potential therapies for mitochondrial diseases. In this review we discuss existing mouse models of mitochondrial complex I dysfunction, focusing on those with similarities to human mitochondrial disorders. We also discuss some of the noteworthy murine genetic models in which complex I genes are not disrupted, but complex I dysfunction is observed, along with some of the more popular chemical compounds that inhibit complex I function and are useful for modeling complex I deficiency in mice. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.