title: Control of mitochondrial integrity in ageing and disease.
abstract: Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a 'healthy' population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria.
authors.affiliation: Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands radek.szklarczyk@maastrichtuniversity.nl.
authors.forename: Radek
authors.initials: R
authors.lastname: Szklarczyk
authors.affiliation: Department of Biochemistry (286), Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Nooteboom
authors.affiliation: Faculty for Biosciences and Cluster of Excellence 'Macromolecular Complexes', Goethe University, Molecular Developmental Biology, 60438 Frankfurt am Main, Germany osiewacz@bio.uni-frankfurt.de.
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins
keywords: ageing; disease; mitochondria; quality control