Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health

• Published in: Biochimica et biophysica acta Vol. 1840; no. 4; pp. 1254 - 1265
• Main Authors: Kotiadis, Vassilios N., Duchen, Michael R., Osellame, Laura D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2014; Elsevier Pub. Co
• Subjects: Animals; antioxidant activity; Antioxidant defence; Autophagy; biochemical pathways; calcium signaling; Cell Nucleus - physiology; defense mechanisms; energy; eukaryotic cells; Homeostasis; Humans; import policies; Mitochondria; Mitochondria - physiology; mitochondrial genome; Mitochondrial Proteins - metabolism; Mitophagy; Oxidative Stress; pathophysiology; Protein Folding; Protein homeostasis; proteins; Proteolysis; Quality control; reactive oxygen species; Reactive Oxygen Species - metabolism; Retrograde signalling; Review; Signal Transduction; transcription (genetics); unfolded protein response; Retrograde signalling; Mitochondria; Protein homeostasis; Mitophagy; Quality control; Antioxidant defence
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.10.041

The maintenance of cell metabolism and homeostasis is a fundamental characteristic of living organisms. In eukaryotes, mitochondria are the cornerstone of these life supporting processes, playing leading roles in a host of core cellular functions, including energy transduction, metabolic and calcium signalling, and supporting roles in a number of biosynthetic pathways. The possession of a discrete mitochondrial genome dictates that the maintenance of mitochondrial ‘fitness’ requires quality control mechanisms which involve close communication with the nucleus. This review explores the synergistic mechanisms that control mitochondrial quality and function and ensure cellular bioenergetic homeostasis. These include antioxidant defence mechanisms that protect against oxidative damage caused by reactive oxygen species, while regulating signals transduced through such free radicals. Protein homeostasis controls import, folding, and degradation of proteins underpinned by mechanisms that regulate bioenergetic capacity through the mitochondrial unfolded protein response. Autophagic machinery is recruited for mitochondrial turnover through the process of mitophagy. Mitochondria also communicate with the nucleus to exact specific transcriptional responses through retrograde signalling pathways. The outcome of mitochondrial quality control is not only reliant on the efficient operation of the core homeostatic mechanisms but also in the effective interaction of mitochondria with other cellular components, namely the nucleus. Understanding mitochondrial quality control and the interactions between the organelle and the nucleus will be crucial in developing therapies for the plethora of diseases in which the pathophysiology is determined by mitochondrial dysfunction. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. •Mitochondria are critical components of the eukaryotic cell, responsible for diverse ranges of functions.•While ROS are damaging in excess amounts, low levels are essential signals in homeostasis.•Mitophagy is a highly regulated form of autophagy regulated by PINK1 and Parkin.•Transcription factors activate and coordinate the expression of both nuclear and mitochondrial genes.