Details

Autor(en) / Beteiligte

• Filadi, Riccardo
• Leal, Nuno Santos
• Schreiner, Bernadette
• Rossi, Alice
• Dentoni, Giacomo
• Pinho, Catarina Moreira
• Wiehager, Birgitta
• Cieri, Domenico
• Calì, Tito
• Pizzo, Paola
• Ankarcrona, Maria

Titel

TOM70 Sustains Cell Bioenergetics by Promoting IP3R3-Mediated ER to Mitochondria Ca2+ Transfer

Ist Teil von

• Current biology, 2018-02, Vol.28 (3), p.369-382.e6

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The mitochondrial translocase of the outer membrane (TOM) is a protein complex that is essential for the post-translational import of nuclear-encoded mitochondrial proteins. Among its subunits, TOM70 and TOM20 are only transiently associated with the core complex, suggesting their possible additional roles within the outer mitochondrial membrane (OMM). Here, by using different mammalian cell lines, we demonstrate that TOM70, but not TOM20, clusters in distinct OMM foci, frequently overlapping with sites in which the endoplasmic reticulum (ER) contacts mitochondria. Functionally, TOM70 depletion specifically impairs inositol trisphosphates (IP3)-linked ER to mitochondria Ca2+ transfer. This phenomenon is dependent on the capacity of TOM70 to interact with IP3-receptors and favor their functional recruitment close to mitochondria. Importantly, the reduced constitutive Ca2+ transfer to mitochondria, observed in TOM70-depleted cells, dampens mitochondrial respiration, affects cell bioenergetics, induces autophagy, and inhibits proliferation. Our data reveal a hitherto unexpected role for TOM70 in pro-survival ER-mitochondria communication, reinforcing the view that the ER-mitochondria signaling platform is a key regulator of cell fate. [Display omitted] •TOM70 clusters at ER-mitochondria contact sites•TOM70 interacts with IP3R3 and recruits it close to mitochondria•TOM70 promotes IP3-dependent ER to mitochondria Ca2+ transfer•Mitochondrial Ca2+ signal promoted by TOM70 sustains cell bioenergetics Filadi et al. show that TOM70, a component of the mitochondrial translocase of the outer membrane, has an IP3R3-dependent but translocase-independent function that sustains cell bioenergetics. TOM70 clusters at ER-mitochondria contacts, recruits IP3R3, and promotes inter-organelle Ca2+ transfer, bioenergetics, and cell proliferation.