title: Mitochondria: Biogenesis and mitophagy balance in segregation and clonal expansion of mitochondrial DNA mutations.
abstract: Mitochondria are cytoplasmic organelles containing their own multi-copy genome. They are organized in a highly dynamic network, resulting from balance between fission and fusion, which maintains homeostasis of mitochondrial mass through mitochondrial biogenesis and mitophagy. Mitochondrial DNA (mtDNA) mutates much faster than nuclear DNA. In particular, mtDNA point mutations and deletions may occur somatically and accumulate with aging, coexisting with the wild type, a condition known as heteroplasmy. Under specific circumstances, clonal expansion of mutant mtDNA may occur within single cells, causing a wide range of severe human diseases when mutant overcomes wild type. Furthermore, mtDNA deletions accumulate and clonally expand as a consequence of deleterious mutations in nuclear genes involved in mtDNA replication and maintenance, as well as in mitochondrial fusion genes (mitofusin-2 and OPA1), possibly implicating mtDNA nucleoids segregation. We here discuss how the intricacies of mitochondrial homeostasis impinge on the intracellular propagation of mutant mtDNA. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.
authors: IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. Electronic address: valerio.carelli@unibo.it.
authors: Valerio
authors: V
authors: Carelli
authors: IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors: Alessandra
authors: A
authors: Maresca
authors: IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors: Leonardo
authors: L
authors: Caporali
authors: Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; Unit of Cellular Biochemistry, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors: Selena
authors: S
authors: Trifunov
authors: IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Unit of Cellular Biochemistry, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors: Claudia
authors: C
authors: Zanna
authors: Unit of Cellular Biochemistry, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors: Michela
authors: M
authors: Rugolo
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000235:genetics; D063306:Mitophagy / Q000235:genetics*; D009154:Mutation; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: Clonal expansion; Mitochondrial DNA; Mitochondrial DNA mutations; Mitophagy; Nucleoids