title: Cardiolipin is a key determinant for mtDNA stability and segregation during mitochondrial stress.
abstract: Mitochondria play a key role in adaptation during stressing situations. Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be a determinant in this adaptive mechanism since it modulates the activity of most membrane proteins. Here, we used Saccharomyces cerevisiae subjected to conditions that affect mitochondrial metabolism as a model to determine the possible role of cardiolipin in stress adaptation. Interestingly, we found that thermal stress promotes a 30% increase in the cardiolipin content and modifies the physical state of mitochondrial membranes. These changes have effects on mtDNA stability, adapting cells to thermal stress. Conversely, this effect is cardiolipin-dependent since a cardiolipin synthase-null mutant strain is unable to adapt to thermal stress as observed by a 60% increase of cells lacking mtDNA (ρ0). Interestingly, we found that the loss of cardiolipin specifically affects the segregation of mtDNA to daughter cells, leading to a respiratory deficient phenotype after replication. We also provide evidence that mtDNA physically interacts with cardiolipin both in S. cerevisiae and in mammalian mitochondria. Overall, our results demonstrate that the mitochondrial lipid cardiolipin is a key determinant in the maintenance of mtDNA stability and segregation.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes, 748, São Paulo, SP 05508-000, Brazil. Electronic address: aluevano@iq.usp.br.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Luévano-Martínez
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes, 748, São Paulo, SP 05508-000, Brazil.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Forni
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes, 748, São Paulo, SP 05508-000, Brazil.
authors.forename: Valquiria Tiago
authors.initials: VT
authors.lastname: dos Santos
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes, 748, São Paulo, SP 05508-000, Brazil.
authors.forename: Nadja C
authors.initials: NC
authors.lastname: Souza-Pinto
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes, 748, São Paulo, SP 05508-000, Brazil.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
mesh_terms: D002308:Cardiolipins / Q000378:metabolism*; D019069:Cell Respiration / Q000502:physiology*; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000737:chemistry* / Q000378:metabolism; D004579:Electron Transport; D031541:Fluorescence Resonance Energy Transfer; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051336:Mitochondrial Membranes / Q000737:chemistry* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010743:Phospholipids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature
chemical_list: D002308:Cardiolipins; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D010743:Phospholipids
keywords: Membrane plasticity; Mitochondrial DNA; Mitochondrion; Phospholipid