Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 5 min ago
Peer-reviewedCC BY 4.0Advanced Science

ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER–Mitochondria Contact Sites

  • Yiru Cheng1
  • Peiyuan Chai1
  • Xiayuhe Pei1
  • Yiwen Chen2
  • Xiaoshuai Huang3
  • Bei Liu4
  • Yiqian Wu4
  • Junlin Teng1
  • Pengli Zheng1,2
  • Jianguo Chen1,5
5 affiliations
  1. 1Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences Peking University Beijing China
  2. 2Center For Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing China
  3. 3Beijing Advanced Center of Cellular Homeostasis and Aging‐Related Diseases, Institute of Advanced Clinical Medicine Peking University Beijing China
  4. 4National Biomedical Imaging Center, College of Future Technology Peking University Beijing China
  5. 5Center for Quantitative Biology Academy for Advanced Interdisciplinary Studies Peking University Beijing China
Read full textDOICite

Abstract

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.

Related

  1. A Novel Drp1-Golph2 Tether Mediates Mitochondria-Golgi Spatial Association to Orchestrate Mitochondrial Function and Hepatic Lipid Catabolism Across Vertebrates
    Guang-Li Feng, Nan-Jun Hu, Ying-Jia Chi +2
    Journal of Biological ChemistryPeer-reviewedCC BY 4.0Molecular biology & gene regulationCrossref
  2. Cardiomyocyte-specific deletion of thioredoxin promotes myocardial injury, infarction and mitochondrial dysfunction: translocation of cytosolic thioredoxin into mitochondria rescue myocardial dysfunction by restoration of cardiac mitochondrial structure and function.
    Sudhir Kumar, Richa Rani, Venkatesh Sridharan +2
    Redox biologyPeer-reviewedCC BY-NC-NDFull textMolecular biology & gene regulationEurope PMC
  3. Mitochondrial genome microhomology-mediated editing by donor DNA delivery into mitochondria in human cells
    Vadim Maximov, Nikita Shebanov, Natalia Nikitchina +5
    Molecular Therapy - Nucleic AcidsPeer-reviewedCC BY 4.0Full text1 citedProteomics & metabolomicsSystems & synthetic biologyHAL
  4. In vivo analyses reveal rapid and permissive lipid transport between the ER and mitochondria
    Paul Montmayeul, Samantha Voguin, Catherine Albrieux +9
    HALPreprintCC BY-NC 4.0Full textEnzymology & metabolismHAL
  5. Nanoscale spatial confinement of proton flux by cardiolipin drives high-speed lateral proton transport in mitochondria
    I. Adeniran, H. Degens
    bioRxivPreprintCC BY-NC-NDFull textBiophysicsbioRxiv

Cite

BibTeXRIS
BibTeX
@article{cheng2026atl2,
  title = {{ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER–Mitochondria Contact Sites}},
  author = {Yiru Cheng and Peiyuan Chai and Xiayuhe Pei and Yiwen Chen and Xiaoshuai Huang and Bei Liu and Yiqian Wu and Junlin Teng and Pengli Zheng and Jianguo Chen},
  journal = {Advanced Science},
  year = {2026},
  month = jul,
  doi = {10.1002/advs.76972},
  url = {https://doi.org/10.1002/advs.76972},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER–Mitochondria Contact Sites
AU  - Yiru Cheng
AU  - Peiyuan Chai
AU  - Xiayuhe Pei
AU  - Yiwen Chen
AU  - Xiaoshuai Huang
AU  - Bei Liu
AU  - Yiqian Wu
AU  - Junlin Teng
AU  - Pengli Zheng
AU  - Jianguo Chen
PY  - 2026
DA  - 2026/07/30
JO  - Advanced Science
DO  - 10.1002/advs.76972
UR  - https://doi.org/10.1002/advs.76972
AB  - 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.
SN  - 2198-3844
ER  -