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

Author(s)

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

Affiliation

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

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS; v. 1847, n. 6-7, p. 587-598, JUN-JUL 2015.
• Web of Science Citations: 17

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 (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)

• FAPESP's process: 10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism
• Grantee: Alicia Juliana Kowaltowski
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/18254-0 - Molecular mechanisms of repair of double strand breaks in mitochondrial DNA
• Grantee: Valquiria Tiago dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/04919-9 - Evaluation of the adaptive response of mitochondrial membranes to stress: role of cardiolipin in membrane plasticity, dynamics and pathological situations
• Grantee: Luis Alberto Luevano Martinez
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/04871-6 - Effects of caloric restriction on mitochondrial morphology, dynamics, bioenergetics and redox state
• Grantee: Maria Fernanda Pereira de Araújo Demonte Forni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC