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Updated: Aug 5, 2026

Study of Endoplasmic Reticulum and Mitochondria Interactions by In Situ Proximity Ligation Assay in Fixed Cells
Published on: December 10, 2016
ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER-Mitochondria Contact Sites
Yiru Cheng1, Peiyuan Chai1, Xiayuhe Pei1
1Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China.
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.
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