ArticleScience advances2017
Cardiolipin mediates membrane and channel interactions of the mitochondrial TIM23 protein import complex receptor Tim50.
Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Genome-Wide Identification and Expression Analysis of the TIM Gene Family in Sea-Island Cotton (Current issues in molecular biology · 2026Article
- Rewiring Lipid Metabolism: PINK1 as a Central Regulator of Mitochondrial Homeostasis in Parkinson's Disease.International journal of molecular sciences · 2026Review
- TRIM59 suppresses mitochondrial-associated apoptosis to facilitate progression in papillary renal cell carcinoma via the ACAT1-cardiolipin pathway.Cell death & disease · 2025Article
- IL-1 protects from fatal systemic candidiasis in mice by inhibiting oxidative phosphorylation and hypoxia.Nature communications · 2025Article
- Aging and Alzheimer's: the critical role of mitochondrial dysfunction and synaptic alterations.Frontiers in synaptic neuroscience · 2025Review
- Facts, Dogmas, and Unknowns About Mitochondrial Reactive Oxygen Species in Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Mitochondrial phospholipid metabolism in health and disease.Journal of cell science · 2023Article
- Mitochondria Have Made a Long Evolutionary Path from Ancient Bacteria Immigrants within Eukaryotic Cells to Essential Cellular Hosts and Key Players in Human Health and Disease.Current issues in molecular biology · 2023Review
- Metabolic sensing and control in mitochondria.Molecular cell · 2023Review
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Advances in methods to analyse cardiolipin and their clinical applications.Trends in analytical chemistry : TRAC · 2022Article
- Review
- Review
- pH-Sensitive Liposomes for Enhanced Cellular Uptake and Cytotoxicity of Daunorubicin in Melanoma (B16-BL6) Cell Lines.Pharmaceutics · 2022Article
- Crosstalk between Mitochondrial Protein Import and Lipids.International journal of molecular sciences · 2022Review
- Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation.The Journal of biological chemistry · 2022Review
- Specific interactions of peripheral membrane proteins with lipids: what can molecular simulations show us?Bioscience reports · 2022Article
- Role of Mitochondrial Protein Import in Age-Related Neurodegenerative and Cardiovascular Diseases.Cells · 2021Review
- Mitochondrial compartmentalization: emerging themes in structure and function.Trends in biochemical sciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The phospholipid cardiolipin mediates the functional interactions of proteins that reside within energy-conserving biological membranes. However, the molecular basis by which this lipid performs this essential cellular role is not well understood. We address this role of cardiolipin using the multisubunit mitochondrial TIM23 protein transport complex as a model system. The early stages of protein import by this complex require specific interactions between the polypeptide substrate receptor, Tim50, and the membrane-bound channel-forming subunit, Tim23. Using analyses performed in vivo, in isolated mitochondria, and in reductionist nanoscale model membrane systems, we show that the soluble receptor domain of Tim50 interacts with membranes and with specific sites on the Tim23 channel in a manner that is directly modulated by cardiolipin. To obtain structural insights into the nature of these interactions, we obtained the first small-angle x-ray scattering-based structure of the soluble Tim50 receptor in its entirety. Using these structural insights, molecular dynamics simulations combined with a range of biophysical measurements confirmed the role of cardiolipin in driving the association of the Tim50 receptor with lipid bilayers with concomitant structural changes, highlighting the role of key structural elements in mediating this interaction. Together, these results show that cardiolipin is required to mediate specific receptor-channel associations in the TIM23 complex. Our results support a new working model for the dynamic structural changes that occur within the complex during transport. More broadly, this work strongly advances our understanding of how cardiolipin mediates interactions among membrane-associated proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.