Ask about this productRelated genes to: TRAK1 antibody
- Gene:
- TRAK1 NIH gene
- Name:
- trafficking kinesin protein 1
- Previous symbol:
- -
- Synonyms:
- OIP106, KIAA1042, MILT1
- Chromosome:
- 3p22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-12-13
- Date modifiied:
- 2016-05-16
Related products to: TRAK1 antibody
Related articles to: TRAK1 antibody
- The cellular distribution of mitochondria in response to stress and local energy needs is governed by the relative activities of the microtubule-based molecular motors kinesin and dynein. The mechanism for switching between these two opposite-polarity microtubule motors remains unknown. In this study, we coupled a cellular synthetic cargo transport assay with AlphaFold2-guided mutagenesis to identify a regulatory helix in the mitochondrial adaptor protein [trafficking kinesin-binding protein (TRAK)] that mediates switching between kinesin- and dynein-driven transport. Differences in the helix sequence explained why two near-identical TRAK isoforms transported mitochondria in predominantly opposite directions. Phosphorylation of the regulatory helix by stress-activated kinases caused the activation of dynein and dissociation of kinesin. Our results reveal a molecular mechanism for coordinating the directional transport of mitochondria in response to intracellular signals. - Source: PubMed
Publication date: 2026/08/06
Gladkova ChristinaPaez-Segala Maria GGrant William PKittisopikul MarkMyers Samuel AWang YuxiaoVale Ronald D - Mitochondrial transport and distribution are crucial for cellular homeostasis, yet whether and how they are regulated by endoplasmic reticulum (ER)-mitochondria contact sites remains unclear. Here, we demonstrate that the ER protein atlastin-2 (ATL2) orchestrates mitochondrial transport and distribution by promoting assembly of the transport machinery at ER-mitochondria contact sites. Mechanistically, ATL2 recruits the adaptor trafficking kinesin-binding protein 1 (TRAK1) to the ER membrane, strengthening the interaction of TRAK1 with the mitochondrial transport adaptor MIRO1 to promote anterograde mitochondrial transport. Loss of ATL2 disrupts this process, leading to perinuclear mitochondrial clustering. We further find that ATL2 stabilizes ER-mitochondria contact sites by interacting with MFN2, providing a platform for mitochondrial transport complex assembly. Moreover, in hypoxia, ATL2 is ubiquitinated at lysine 567 by the E3 ligase SYVN1, leading to its degradation and a resulting defect in mitochondrial distribution. Our findings elucidate a novel ER-mediated mechanism for mitochondrial transport. - Source: PubMed
Publication date: 2026/07/30
Cheng YiruChai PeiyuanPei XiayuheChen YiwenHuang XiaoshuaiLiu BeiWu YiqianTeng JunlinZheng PengliChen Jianguo - Sepsis is an immune dysregulation syndrome triggered by infection, characterized by host self-damage due to immune imbalances. This study focuses on dynamic changes of mitochondrial symbiotic function in host cells during sepsis and systematically investigates dysregulation of mitochondrial communication modes and the intrinsic link between mitochondrial DNA (mtDNA) release and immune dysregulation. We demonstrate that during early-stage LPS treatment, mitochondria actively remodel by extruding flagella-like extensions (termed mitoFLARE). These structures, nanotubes mediating long-distance transport, form through glycosylated TRAK1 binding FHL2 to drive actin network formation, thereby shifting mitochondrial communication from direct fusion to nanotube-mediated transport. This helps maintain dynamic exchange within the inner mitochondrial membrane under LPS treatment. However, as inflammation progresses, deteriorated mitochondrial quality control disrupts the MICOS-SAM complex, abrogates inner-outer membrane anchoring, and suppresses mitoFLARE functions. All these ultimately enhance endoplasmic reticulum-mitochondrial contacts to promote outer membrane rupture and result in mtDNA release into the cytoplasm to activate cGAS-STING signaling, further triggering immune dysregulation and inflammatory storm, culminating in programmed cell death and organ dysfunction. This study elucidates the pivotal role of dysregulated mitochondrial-host symbiosis in sepsis progression and provides important insights into the underlying mechanisms of sepsis-associated immune imbalances, laying a theoretical foundation for targeted therapy development. - Source: PubMed
Publication date: 2026/05/25
Hong WeilongMa RuiyanLong ShiyunSong RuiRen ShuangRan XiaopingWan JunfangLiu YifeiLi XiaofengChen QianMa DaqingZhang ZhaocaiHuang HeAshrafizadeh MiladConde JoãoLiu LiangmingDuan Chenyang - Neuronal signaling requires large amounts of ATP, making neurons particularly sensitive to defects in energy homeostasis. Mitochondrial movement and energy production are therefore regulated to align local demands with mitochondrial output. Here, we report a pathway that arrests mitochondria in response to decreases in the ATP-to-AMP ratio, an indication that ATP consumption exceeds supply. In neurons and cell lines, low concentrations of the electron transport chain inhibitor antimycin A decrease the production of ATP and concomitantly arrest mitochondrial movement without triggering mitophagy. This arrest is accompanied by the accumulation of actin fibers adjacent to the mitochondria, which serve as an anchor that resists the associated motors. This arrest is mediated by activation of the energy-sensing kinase AMPK, which phosphorylates TRAK1. This mechanism likely helps maintain cellular energy homeostasis by anchoring energy-producing mitochondria in places where they are most needed. - Source: PubMed
Publication date: 2026/01/30
Falk Jill EHenke TobiasGowrisankaran SindhujaWanderoy SimoneBasu HimanishGreally SineadSteen JudithSchwarz Thomas L - Hypoxia and mitochondrial dysfunction have been implicated in recurrent spontaneous abortion (RSA), although the precise molecular mechanisms remain unclear. This study aimed to explore hypoxia- and mitochondria-related genes (HRGs and MRGs) that may be associated with RSA using integrative bioinformatics approaches and preliminary experimental validation. - Source: PubMed
Publication date: 2025/12/19
Chen LinWei CainiGao LiliLu Dongyang