title: Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cell and Developmental Biology, University College London, WC1E 6BT, UK; UCL Consortium for Mitochondrial Research, University College London, WC1E 6BT, UK.
authors.forename: Vassilios N
authors.initials: VN
authors.lastname: Kotiadis
authors.affiliation: Department of Cell and Developmental Biology, University College London, WC1E 6BT, UK; UCL Consortium for Mitochondrial Research, University College London, WC1E 6BT, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duchen
authors.affiliation: Department of Cell and Developmental Biology, University College London, WC1E 6BT, UK; UCL Consortium for Mitochondrial Research, University College London, WC1E 6BT, UK. Electronic address: l.osellame@latrobe.edu.au.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Osellame
mesh_terms: D000818:Animals; D001343:Autophagy; D002467:Cell Nucleus / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D017510:Protein Folding; D059748:Proteolysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species
keywords: Antioxidant defence; Mitochondria; Mitophagy; Protein homeostasis; Quality control; Retrograde signalling