Your browser doesn't support javascript.
loading
Functional diversity among cardiolipin binding sites on the mitochondrial ADP/ATP carrier.
Senoo, Nanami; Chinthapalli, Dinesh K; Baile, Matthew G; Golla, Vinaya K; Saha, Bodhisattwa; Oluwole, Abraham O; Ogunbona, Oluwaseun B; Saba, James A; Munteanu, Teona; Valdez, Yllka; Whited, Kevin; Sheridan, Macie S; Chorev, Dror; Alder, Nathan N; May, Eric R; Robinson, Carol V; Claypool, Steven M.
Afiliación
  • Senoo N; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Chinthapalli DK; Mitochondrial Phospholipid Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Baile MG; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QU, UK.
  • Golla VK; Kavli Institute for Nanoscience Discovery, Oxford, OX1 3QU, UK.
  • Saha B; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Oluwole AO; Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, 06269, USA.
  • Ogunbona OB; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
  • Saba JA; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QU, UK.
  • Munteanu T; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QU, UK.
  • Valdez Y; Kavli Institute for Nanoscience Discovery, Oxford, OX1 3QU, UK.
  • Whited K; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Sheridan MS; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Chorev D; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Alder NN; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • May ER; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Robinson CV; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Claypool SM; Mitochondrial Phospholipid Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
EMBO J ; 43(14): 2979-3008, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38839991
ABSTRACT
Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved. Here, we investigated the role of these buried CLs in AAC/ANT using a combination of biochemical approaches, native mass spectrometry, and molecular dynamics simulations. We introduced negatively charged mutations into each CL-binding site of yeast Aac2 and established experimentally that the mutations disrupted the CL interactions. While all mutations destabilized Aac2 tertiary structure, transport activity was impaired in a binding site-specific manner. Additionally, we determined that a disease-associated missense mutation in one CL-binding site in human ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Translocasas Mitocondriales de ADP y ATP / Cardiolipinas / Proteínas de Saccharomyces cerevisiae Límite: Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Translocasas Mitocondriales de ADP y ATP / Cardiolipinas / Proteínas de Saccharomyces cerevisiae Límite: Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido