ArticleThe EMBO journal2024
Functional diversity among cardiolipin binding sites on the mitochondrial ADP/ATP carrier.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Angiogenin mediates cell-cell fusion as a mitochondrial RNA processing enzyme.Bone research · 2026Article
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- hUCMSC mitochondrial EVs confer neuroprotection after ischemia by Tom1l2-mediated mitochondrial fusion and Crls1-cardiolipin axis reprogramming.Redox biology · 2026Article
- Disturbed mitochondrial maturation in cardiolipin remodeling-deficient cardiomyocytes.iScience · 2026Article
- Alkyltriphenylphosphonium Binding to Cardiolipin Triggers Oncosis in Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- USP34 attenuates cartilage degradation in temporomandibular joint osteoarthritis by ANT1-mediated mitophagy.JBMR plus · 2026Article
- Unveiling Specificity, Redundancy, and Promiscuity of FiveInternational journal of molecular sciences · 2026Article
- Biogenesis and function of the mitochondrial solute carrier (SLC25) family in yeast.Biological chemistry · 2025Review
- Onion-Mitochondria Inhibit Lipopolysaccharide-Induced Acute Lung Injury by Shaping Lung Macrophage Mitochondrial Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The peculiar properties of mitochondrial carriers of the SLC25 family.The Biochemical journal · 2025Review
- Molecular Dynamics Simulations of a Putative Novel Mechanism for UCP1-Assisted FA Anion Transport.Acta physiologica (Oxford, England) · 2025Article
- Article
- Cardiolipin's multifaceted role in immune response: a focus on interacting proteins.Frontiers in immunology · 2025Review
- Specific Substrate Activity of Lotus Root Polyphenol Oxidase: Insights from Gaussian-Accelerated Molecular Dynamics and Markov State Models.International journal of molecular sciences · 2024Article
- Mitochondrial membrane lipids in the regulation of bioenergetic flux.Cell metabolism · 2024Review
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17 authors.
Funding
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.
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