Fuente: Biomolecules - Revista científica (MDPI) Biomolecules, Vol. 16, Pages 704: Exploring Replicative Senescence and Oxidative Stress-Induced Remodelling of Mitochondrial-Associated Membranes in Human Skin Fibroblasts
Biomolecules doi: 10.3390/biom16050704
Authors:
Anne-Laure Bulteau
Gallic Beauchef
Stéphanie Chanon
Aurélie Vieille-Marchis
Julien Chlasta
Gaël Runel
Juliette Sage
Tanesha Naiken
Lauren Sobilo
Elodie Bossard
Lorene Gourguillon
Carine Nizard
Karl Pays
Laurence Canaple
Beatrice Morio

(1) Background: Calcium transfer between the endoplasmic reticulum (ER) and mitochondria through the IP3R–VDAC1 complex at mitochondria-associated ER membranes (MAMs) is essential for cellular homeostasis. Alterations in this signalling axis have been implicated in ageing and cellular senescence. (2) Methods: We developed an in vitro human dermal fibroblast (HDF) model combining replicative senescence and acute oxidative stress to investigate the role of ER–mitochondria coupling in skin ageing and to enable biomolecule screening. (3) Results: In situ proximity ligation assays revealed that replicative senescence significantly increased the number of VDAC1/IP3R complexes per cell (+85% and +72%, p < 0.01), together with elevated cellular reactive oxygen species (+47% and +74%, p < 0.05). Consistently, acute oxidative stress (50 µM t-BHP, 30 min) rapidly increased VDAC1/IP3R complexes (+48%, p < 0.001) and intra-mitochondrial calcium levels (+19%, p < 0.001). These effects persisted for 24 h post-treatment and were associated with impaired mitochondrial function (−27% in the Bioenergetic Health Index, p < 0.05). We also established a flexibility index capturing both acute and long-term adaptations and detecting the protective effects of an orchid extract. (4) Conclusions: ER–mitochondria coupling disruption via the IP3R–VDAC1 complex may contribute to oxidative stress-induced senescence and represent a key mechanism in extrinsic skin ageing.