{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:43:01Z","timestamp":1775889781016,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,25]]},"group-title":"Genetics","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:00:00Z","timestamp":1737763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Mitochondria control cellular metabolism, serve as hubs for signaling and organelle communication, and are important for the health and survival of cells.\n                  <jats:italic>VPS13D<\/jats:italic>\n                  encodes a cytoplasmic lipid transfer protein that regulates mitochondrial morphology, mitochondria and endoplasmic reticulum (ER) contact, quality control of mitochondria.\n                  <jats:italic>VPS13D<\/jats:italic>\n                  mutations have been reported in patients displaying ataxic and spastic gait disorders with variable age of onset. Here we used CRISPR\/Cas9 gene editing to create\n                  <jats:italic>VPS13D<\/jats:italic>\n                  related-spinocerebellar ataxia-4 (SCAR4) missense mutations and C-terminal deletion in\n                  <jats:italic>VPS13D<\/jats:italic>\n                  \u2019s orthologue\n                  <jats:italic>vps-13D<\/jats:italic>\n                  in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  . Consistent with SCAR4 patient movement disorders and mitochondrial dysfunction,\n                  <jats:italic>vps-13D<\/jats:italic>\n                  mutant worms exhibit locomotion defects and abnormal mitochondrial morphology. Importantly, animals with a\n                  <jats:italic>vps-13D<\/jats:italic>\n                  deletion or a N3017I missense mutation exhibited an increase in mitochondrial unfolded protein response (UPR\n                  <jats:sup>mt<\/jats:sup>\n                  ). The cellular and behavioral changes caused by\n                  <jats:italic>VPS13D<\/jats:italic>\n                  mutations in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  advance the development of animal models that are needed to study SCAR4 pathogenesis.\n                <\/jats:p>","DOI":"10.1101\/2025.01.22.634397","type":"posted-content","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T21:45:14Z","timestamp":1737841514000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>VPS13D<\/i>\n                  mutations affect mitochondrial homeostasis and locomotion in\n                  <i>Caenorhabditis elegans<\/i>"],"prefix":"10.64898","author":[{"given":"Xiaomeng","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"},{"name":"Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605 USA"},{"name":"School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605 USA"},{"name":"School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Thackeray","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric H.","family":"Baehrecke","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1311-5179","authenticated-orcid":false,"given":"Mark J.","family":"Alkema","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041022443498000_2025.01.22.634397v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2024.108271"},{"key":"2026041022443498000_2025.01.22.634397v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.01.010"},{"key":"2026041022443498000_2025.01.22.634397v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.11.064"},{"key":"2026041022443498000_2025.01.22.634397v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-023-02044-y"},{"key":"2026041022443498000_2025.01.22.634397v1.5","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.106.061580"},{"key":"2026041022443498000_2025.01.22.634397v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.01.012"},{"key":"2026041022443498000_2025.01.22.634397v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03024-5"},{"key":"2026041022443498000_2025.01.22.634397v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.04.021"},{"key":"2026041022443498000_2025.01.22.634397v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.12.001"},{"key":"2026041022443498000_2025.01.22.634397v1.10","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-022-02553-0"},{"key":"2026041022443498000_2025.01.22.634397v1.11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063274"},{"key":"2026041022443498000_2025.01.22.634397v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s004380100523"},{"key":"2026041022443498000_2025.01.22.634397v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0023-6"},{"key":"2026041022443498000_2025.01.22.634397v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101601"},{"key":"2026041022443498000_2025.01.22.634397v1.15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010091"},{"key":"2026041022443498000_2025.01.22.634397v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.08.010"},{"key":"2026041022443498000_2025.01.22.634397v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25204"},{"key":"2026041022443498000_2025.01.22.634397v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100748"},{"key":"2026041022443498000_2025.01.22.634397v1.19","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202001042"},{"key":"2026041022443498000_2025.01.22.634397v1.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008638"},{"key":"2026041022443498000_2025.01.22.634397v1.21","doi-asserted-by":"crossref","unstructured":"Haeussler, S. , A. 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