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More recently, dynamic association between them has been identified in different eukaryotes; these interactions vary in their composition and involvement in regulation of intracellular machineries. FAM134B (also known as RETREG1), originally identified as an oncogene, regulates ER membrane shape and curvature. It is a key ER-phagy or reticulophagy receptor, which promotes autophagy of not only the ER but also simultaneous dual autophagy of ER and mitochondria. Although it is known that FAM134B can potentiate contact with mitochondria, its direct involvement in affecting mitochondrial dynamics remains unexplored. Here, we show that FAM134B can interact with the canonical fission-promoting protein DRP1 (also known as DNM1L). Functional depletion of FAM134B leads to local actin rearrangement and reduced DRP1 recruitment onto mitochondria, resulting in hyperfusion. A decrease in FAM134B levels is observed with aging in rat brains, cell and mouse models of Parkinson's disease and samples derived from individuals with disease. Our study establishes FAM134B as the ER partner that helps in maintaining mitochondrial morphology and dynamics.<\/jats:p>","DOI":"10.1242\/jcs.263920","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:43:50Z","timestamp":1762163030000},"source":"Crossref","is-referenced-by-count":2,"title":["The endoplasmic reticulum protein FAM134B acts as a regulator of mitochondrial morphology"],"prefix":"10.1242","volume":"138","author":[{"given":"Sebabrata","family":"Maity","sequence":"first","affiliation":[{"name":"Saha Institute of Nuclear Physics 1 Biophysics & Structural Genomics Division , , 1\/AF Bidhannagar, Kolkata 700064, WB ,","place":["India"]},{"name":"Homi Bhabha National Institute 2 , Mumbai 400094, Maharashtra ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwesha","family":"Dutta Gupta","sequence":"additional","affiliation":[{"name":"Saha Institute of Nuclear Physics 1 Biophysics & Structural Genomics Division , , 1\/AF Bidhannagar, Kolkata 700064, WB ,","place":["India"]},{"name":"Homi Bhabha National Institute 2 , Mumbai 400094, Maharashtra ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izaz Monir","family":"Kamal","sequence":"additional","affiliation":[{"name":"CSIR Indian Institute of Chemical Biology 3 Structural Biology and Bioinformatics Division , , CN 6, Sector V, Salt Lake, Kolkata 700091 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) 4 , Ghaziabad 201002, UP ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajdeep","family":"Das","sequence":"additional","affiliation":[{"name":"Saha Institute of Nuclear Physics 1 Biophysics & Structural Genomics Division , , 1\/AF Bidhannagar, Kolkata 700064, WB ,","place":["India"]},{"name":"Homi Bhabha National Institute 2 , Mumbai 400094, Maharashtra ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupsha","family":"Mondal","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) 4 , Ghaziabad 201002, UP ,","place":["India"]},{"name":"CSIR-Indian Institute of Chemical Biology 5 Cell Biology and Physiology Division , , IICB TRUE Campus, CN-6, Sector 5, Salt Lake, Kolkata 700091, WB ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpit","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) 4 , Ghaziabad 201002, UP ,","place":["India"]},{"name":"CSIR\u2013Institute of Microbial Technology 6 , Sector-39A, Chandigarh 160036 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Sharma","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) 4 , Ghaziabad 201002, UP ,","place":["India"]},{"name":"CSIR\u2013Institute of Microbial Technology 6 , Sector-39A, Chandigarh 160036 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) 4 , Ghaziabad 201002, UP ,","place":["India"]},{"name":"CSIR-Indian Institute of Chemical Biology 5 Cell Biology and Physiology Division , , IICB TRUE Campus, CN-6, Sector 5, Salt Lake, Kolkata 700091, WB ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saikat","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"CSIR Indian Institute of Chemical Biology 3 Structural Biology and Bioinformatics Division , , CN 6, Sector V, Salt Lake, Kolkata 700091 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) 4 , Ghaziabad 201002, UP ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1509-3679","authenticated-orcid":false,"given":"Oishee","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Saha Institute of Nuclear Physics 1 Biophysics & Structural Genomics Division , , 1\/AF Bidhannagar, Kolkata 700064, WB ,","place":["India"]},{"name":"Homi Bhabha National Institute 2 , Mumbai 400094, Maharashtra ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"2025112006193966000_JCS263920C1","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1038\/s41598-020-58505-6","article-title":"Fibroblast mitochondria in idiopathic Parkinson's disease display morphological changes and enhanced resistance to depolarization","volume":"10","author":"Antony","year":"2020","journal-title":"Sci. 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