TY - JOUR TI - An ER phospholipid hydrolase drives ER-associated mitochondrial constriction for fission and fusion AU - Nguyen, Tricia T AU - Voeltz, Gia K A2 - Schekman, Randy A2 - Kornmann, Benoît A2 - Schekman, Randy VL - 11 PY - 2022 DA - 2022/11/30 SP - e84279 C1 - eLife 2022;11:e84279 DO - 10.7554/eLife.84279 UR - https://doi.org/10.7554/eLife.84279 AB - Mitochondria are dynamic organelles that undergo cycles of fission and fusion at a unified platform defined by endoplasmic reticulum (ER)-mitochondria membrane contact sites (MCSs). These MCSs or nodes co-localize fission and fusion machinery. We set out to identify how ER-associated mitochondrial nodes can regulate both fission and fusion machinery assembly. We have used a promiscuous biotin ligase linked to the fusion machinery, Mfn1, and proteomics to identify an ER membrane protein, ABHD16A, as a major regulator of node formation. In the absence of ABHD16A, fission and fusion machineries fail to recruit to ER-associated mitochondrial nodes, and fission and fusion rates are significantly reduced. ABHD16A contains an acyltransferase motif and an α/β hydrolase domain, and point mutations in critical residues of these regions fail to rescue the formation of ER-associated mitochondrial hot spots. These data suggest a mechanism whereby ABHD16A functions by altering phospholipid composition at ER-mitochondria MCSs. Our data present the first example of an ER membrane protein that regulates the recruitment of both fission and fusion machineries to mitochondria. KW - endoplasmic reticulum KW - mitochondria KW - organelle contact sites KW - membrane fission KW - membrane fusion JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -