Biogenesis of NDUFS3-less complex I indicates TMEM126A/OPA7 as an assembly factor of the ND4-module [article]

Luigi D'Angelo, Elisa Astro, Monica De Luise, Ivana Kurelac, Nikkitha Umesh-Ganesh, Shujing Ding, Ian M. Fearnley, Massimo Zeviani, Giuseppe Gasparre, Anna Maria Porcelli, Erika Fernandez-Vizarra, Luisa Iommarini
2020 bioRxiv   pre-print
Complex I (CI) is the largest enzyme of the mitochondrial respiratory chain and its defects constitute the principal cause of mitochondrial disease. To understand the mechanisms regulating the extremely intricate biogenesis of this fundamental bioenergetic machine, we dissected the structural and functional consequences of the depletion of NDUFS3, a non-catalytic core subunit. We prove that in diverse cell contexts a small, but still detectable, proportion of functional CI can still be found in
more » ... the absence of NDUFS3. In addition, we have determined the dynamics of disassembly of CI when the amounts of NDUFS3 are gradually decreased. The process of degradation of the complex occurs in a hierarchical and modular fashion where the ND4-module remains stable and bound to TMEM126A. We have thus, uncovered the function of TMEM126A, the product of a disease gene causing optic atrophy, as a factor necessary for the correct assembly and function of CI.
doi:10.1101/2020.10.22.350587 fatcat:ro65modylfbgbeq7ugb6mdmxeq