ATAD3 is a limiting factor in mitochondrial biogenesis and adipogenesis of white adipocyte‐like 3T3‐L1 cells - Université Grenoble Alpes
Article Dans Une Revue Cell Biology International Année : 2024

ATAD3 is a limiting factor in mitochondrial biogenesis and adipogenesis of white adipocyte‐like 3T3‐L1 cells

Shuijie Li
  • Fonction : Auteur
Rui Xu
  • Fonction : Auteur
Yao Yao
  • Fonction : Auteur

Résumé

ATAD3 is a vital ATPase of the inner mitochondrial membrane of pluri-cellular eukaryotes, with largely unknown functions but early required for organism development as necessary for mitochondrial biogenesis. ATAD3 knock-down in C. elegans inhibits at first the development of adipocyte-like intestinal tissue so we used mouse adipocyte model 3T3-L1 cells to analyze ATAD3 functions during adipogenesis and lipogenesis in a mammalian model. ATAD3 function was studied by stable and transient modulation of ATAD3 expression in adipogenesis-induced 3T3-L1 cells using Knock-Down and overexpression strategies, exploring different steps of adipocyte differentiation and lipogenesis. We show that (i) an increase in ATAD3 is preceding differentiation-induced mitochondrial biogenesis; (ii) downregulation of ATAD3 inhibits adipogenesis, lipogenesis, and impedes overexpression of many mitochondrial proteins; (iii) ATAD3 re-expression rescues the phenotype of ATAD3 KD, and (iv) differentiation and lipogenesis are accelerated by ATAD3 overexpression, but inhibited by expression of a dominant-negative mutant. We further show that the ATAD3 KD phenotype is not due to altered insulin signal but involves a limitation of mitochondrial biogenesis linked to Drp1. These results demonstrate that ATAD3 is limiting for in vitro mitochondrial biogenesis and adipogenesis/lipogenesis and therefore that ATAD3 mutation/over-or underexpression could be involved in adipogenic and lipogenic pathologies.

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Dates et versions

hal-04736717 , version 1 (15-10-2024)

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Shuijie Li, Rui Xu, Yao Yao, Denis Rousseau. ATAD3 is a limiting factor in mitochondrial biogenesis and adipogenesis of white adipocyte‐like 3T3‐L1 cells. Cell Biology International, 2024, 48, pp.1473 - 1489. ⟨10.1002/cbin.12206⟩. ⟨hal-04736717⟩
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