Cell reports · 2022
Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Combot Yoann, Salo Veijo T, Chadeuf Gilliane, Hölttä Maarit, Ven Katharina, Pulli Ilari, Ducheix Simon, Pecqueur Claire, Renoult Ophélie, Lak Behnam, Li Shiqian, Karhinen Leena, Belevich Ilya, Le May Cedric, Rieusset Jennifer, Le Lay Soazig, Croyal Mikael, Tayeb Karim Si, Vihinen Helena, Jokitalo Eija, Törnquist Kid, Vigouroux Corinne, Cariou Bertrand, Magré Jocelyne, Larhlimi Abdelhalim, Ikonen Elina, Prieur Xavier
Аннотация
Deficiency of the endoplasmic reticulum (ER) protein seipin results in generalized lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities in seipin-deficient patient cells. A subset of seipin is enriched at ER-mitochondria contact sites (MAMs) in human and mouse cells and localizes in the vicinity of calcium regulators SERCA2, IP3R, and VDAC. Seipin association with MAM calcium regulators is stimulated by fasting-like stimuli, while seipin association with lipid droplets is promoted by lipid loading. Acute seipin removal does not alter ER calcium stores but leads to defective mitochondrial calcium import accompanied by a widespread reduction in Krebs cycle metabolites and ATP levels. In mice, inducible seipin deletion leads to mitochondrial dysfunctions preceding the development of metabolic complications. Together, these data suggest that seipin controls mitochondrial energy metabolism by regulating mitochondrial calcium influx at MAMs. In seipin-deficient adipose tissue, reduced ATP production compromises adipocyte properties, contributing to lipodystrophy pathogenesis.