Cardiolipin is a key determinant for mtDNA stability and segregation during mitochondrial stress

Autor(es)

Luevano-Martinez, Luis Alberto ^[1] ; Forni, Maria Fernanda ^[1] ; dos Santos, Valquiria Tiago ^[1] ; Souza-Pinto, Nadja C. ^[1] ; Kowaltowski, Alicia J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS; v. 1847, n. 6-7, p. 587-598, JUN-JUL 2015.
• Citações Web of Science: 17
• Assunto(s): DNA mitocondrial Mitocôndrias Saccharomyces cerevisiae

Resumo

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 (rho(0)). 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. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 13/04919-9 - Avaliação da resposta adaptativa das membranas mitocondriais em situações de estresse: papel da cardiolipina na plasticidade da membrana, dinâmica e situações patológicas
• Beneficiário: Luis Alberto Luevano Martinez
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 10/18254-0 - Estudo dos mecanismos moleculares do reparo de quebra de duplas fitas no DNA mitocondrial
• Beneficiário: Valquiria Tiago dos Santos
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/04871-6 - Efeitos da restrição calórica sobre a morfologia, dinâmica, bioenergética e estado redox mitocondriais
• Beneficiário: Maria Fernanda Pereira de Araújo Demonte Forni
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/51906-1 - Bioenergética, transporte iônico, balanço redox e metabolismo de DNA em mitocôndrias
• Beneficiário: Alicia Juliana Kowaltowski
• Linha de fomento: Auxílio à Pesquisa - Temático