Structural Basis of Tom1-Tollip Complex Assembly in Directing Parkin Perinuclear Clustering on Depolarized Mitochondria

Structural Basis of Tom1-Tollip Complex Assembly in Directing Parkin Perinuclear Clustering on Depolarized Mitochondria | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Structural Basis of Tom1-Tollip Complex Assembly in Directing Parkin Perinuclear Clustering on Depolarized Mitochondria Yingli Wang, Xiao Tao, You wei Xu, Yongzheng Zhang, Chenran Lin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9067593/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Efficient elimination of dysfunctional mitochondria is a central aspect of mitochondrial quality control (MQC) and is essential for maintaining cellular homeostasis. This process relies on the E3 ubiquitin ligase Parkin, which is recruit by phos-ubiquitin and undergo critical spatial redistribution to cluster around damaged mitochondria in the perinuclear region. While Parkin's initial recruitment to depolarized mitochondria is well-studied, the molecular mechanisms that modulate its higher-order spatial organization and perinuclear clustering remain poorly defined. Here, we identify the Tom1-Tollip complex plays a pivotal role for Parkin clustering. By present the first high-resolution crystal structure of the Tom1/GAT-Tollip/TBD complex, we providing atomic-level insight into the stable assembly and functional architecture of this complex. We demonstrate that this complex is critical for MQC by facilitating Parkin into perinuclear clusters required for efficient mitochondrial enclosure and clearance. Loss of either Tom1 or Tollip, or disruption of their direct interaction, severely impairs Parkin's characteristic perinuclear clustering and obstructs damaged mitochondria elimination. Our findings illuminate a previously unappreciated function of the Tom1-Tollip complex in orchestrating the spatial organization of Parkin, thereby influencing the efficient clearance of damaged mitochondria during stress conditions. Biological sciences/Biophysics Biological sciences/Cell biology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supportinginformation.pdf Supporting Data SupportingVideo2BTom1KOCCCPAcGFPTollip.avi Tollip mitochondrial trafficking is impaired in Tom1KO cells under mitochondria stress SupportingVideo4BTom1KOCCCPmCherryParkin.avi Parkin perinuclear translocation is impaired in Tom1KO cells under mitochondrial stress SupportingVideo2ATom1KOAOAcGFPTollip.avi Tollip mitochondrial trafficking is impaired in Tom1KO cells under mitochondria stress SupportingVideo1AWTAOAcGFPTollip.avi Mitochondrial stress induces dynamic Tollip redistribution in live cells SupportingVideo3AWTAOmCherryParkin.avi itochondrial stress induces Parkin perinuclear translocation in live cells SupportingVideo4ATom1KOAOmCherryParkin.avi Parkin perinuclear translocation is impaired in Tom1KO cells under mitochondrial stress SupportingVideo3BWTCCCPmCherryParkin.avi itochondrial stress induces Parkin perinuclear translocation in live cells SupportingVideo1BWTCCCPAcGFPTollip.avi Mitochondrial stress induces dynamic Tollip redistribution in live cells SupportingVideo6Tom1KOTetOnCCCPAcGFPTollip.avi Restoration of Tom1 expression rescues stress-induced Tollip mitochondrial trafficking SupportingVideo5Tom1KOTetOnCCCPAcGFPTollip.avi Depletion of Tom1 impairs mitochondrial trafficking of Tollip Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9067593","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":609364144,"identity":"485979d9-3e65-4687-878a-8efe92f431f7","order_by":0,"name":"Yingli 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