Glytsou 2015 Abstract MiPschool London 2015
|Nitric oxide-associated 1 (NOA1) is part of the OPA1 complexes targeted during cell death.|
Event: MiPschool London 2015
Mitochondria are key regulators of programmed cell death, during which their shape and ultrastructure change, contributing to the mobilization of the cristae-endowed cytochrome c to the intermembrane space and eventually to the cytosol . This process of cristae remodeling is controlled by Optic Atrophy 1 (OPA1), an inner mitochondrial membrane protein, whose complexes are disrupted early during apoptosis .
Blue Native PAGE followed by LC/MS analysis in heart mitochondria extracts revealed that nitric oxide-associated 1 (NOA1) is a candidate partner of OPA1-containing complexes. NOA1 is a newly characterized mitochondrial GTPase [3,4], but its precise function is poorly understood. NOA1 is a peripheral membrane protein, located within the inner mitochondrial compartments. Blue Native PAGE of isolated mitochondria confirmed that NOA1 and OPA1 share same complexes. Moreover, OPA1 and NOA1 genetically interact, since OPA1 is up-regulated in Noa1 deficient MEFs, and NOA1 lacks in Opa1 deficient MEFs. Deficiency of NOA1 leads to mitochondrial fragmentation and cristae disorganization, which is corrected by OPA1 overexpression to a similar extent as upon re-introduction of NOA1, further supporting that OPA1 and NOA1 interplay in the regulation of cristae shape. Functionally, seahorse experiments and cytofluorimetry indicate that NOA1 is an essential protein for oxidative phosphorylation, apoptosis and mitochondria-dependent cell growth. In conclusion, NOA1 is a novel partner of OPA1 in the regulation of mitochondrial ultrastructure and function.
Labels: MiParea: mt-Structure;fission;fusion
1-Fondazione S. Lucia IRCCS, Roma, Italy. - [email protected]
2-Dept Biol, Univ Padova, Italy
3-Dulbecco-Telethon Inst, Fondazione Telethon, Italy
4-Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain
5-Venetian Inst Molecular Medicine (VIMM), Padova, Italy
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