Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes

Yoann Combot, Veijo T Salo, Gilliane Chadeuf, Maarit Hölttä, Katharina Ven, Ilari Pulli, Simon Ducheix, Claire Pecqueur, Ophélie Renoult, Behnam Lak, Shiqian Li, Leena Karhinen, Ilya Belevich, Cedric Le May, Jennifer Rieusset, Soazig Le Lay, Mikael Croyal, Karim Si Tayeb, Helena Vihinen, Eija JokitaloKid Törnquist, Corinne Vigouroux, Bertrand Cariou, Jocelyne Magré, Abdelhalim Larhlimi, Elina Ikonen, Xavier Prieur

Research output: Contribution to journalArticleScientificpeer-review

18 Citations (Scopus)
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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.

Original languageEnglish
Article number110213
Number of pages25
JournalCell Reports
Issue number2
Publication statusPublished - 11 Jan 2022
MoE publication typeA1 Journal article-refereed


  • Adipocytes/metabolism
  • Adipose Tissue/metabolism
  • Animals
  • Calcium/metabolism
  • Cell Line
  • Endoplasmic Reticulum/metabolism
  • Endoplasmic Reticulum Stress
  • Energy Metabolism/physiology
  • GTP-Binding Protein gamma Subunits/deficiency
  • Humans
  • Lipid Droplets/metabolism
  • Lipid Metabolism/physiology
  • Lipids/physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria/metabolism


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