Complex I (CI) is the largest enzyme of the mitochondrial respiratory chain, and its defects are the main cause of mitochondrial disease. To understand the mechanisms regulating the extremely intricate biogenesis of this fundamental bioenergetic machine, we analyze the structural and functional consequences of the ablation of NDUFS3, a non-catalytic core subunit. We show that, in diverse mammalian cell types, a small amount of functional CI can still be detected in the complete absence of NDUFS3. In addition, we determine the dynamics of CI disassembly when the amount of NDUFS3 is gradually decreased. The process of degradation of the complex occurs in a hierarchical and modular fashion in which the ND4 module remains stable and bound to TMEM126A. We, thus, uncover the function of TMEM126A, the product of a disease gene causing recessive optic atrophy as a factor necessary for the correct assembly and function of CI.

NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate / D’Angelo, Luigi; Astro, Elisa; De Luise, Monica; Kurelac, Ivana; Umesh-Ganesh, Nikkitha; Ding, Shujing; Fearnley, Ian M.; Gasparre, Giuseppe; Zeviani, Massimo; Porcelli, Anna Maria; Fernandez-Vizarra, Erika; Iommarini, Luisa. - In: CELL REPORTS. - ISSN 2211-1247. - ELETTRONICO. - 35:3(2021), pp. 109002.1-109002.21. [10.1016/j.celrep.2021.109002]

NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate

D’Angelo, Luigi;Astro, Elisa;De Luise, Monica;Kurelac, Ivana;Umesh-Ganesh, Nikkitha;Gasparre, Giuseppe;Porcelli, Anna Maria;Iommarini, Luisa
2021

Abstract

Complex I (CI) is the largest enzyme of the mitochondrial respiratory chain, and its defects are the main cause of mitochondrial disease. To understand the mechanisms regulating the extremely intricate biogenesis of this fundamental bioenergetic machine, we analyze the structural and functional consequences of the ablation of NDUFS3, a non-catalytic core subunit. We show that, in diverse mammalian cell types, a small amount of functional CI can still be detected in the complete absence of NDUFS3. In addition, we determine the dynamics of CI disassembly when the amount of NDUFS3 is gradually decreased. The process of degradation of the complex occurs in a hierarchical and modular fashion in which the ND4 module remains stable and bound to TMEM126A. We, thus, uncover the function of TMEM126A, the product of a disease gene causing recessive optic atrophy as a factor necessary for the correct assembly and function of CI.
2021
NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate / D’Angelo, Luigi; Astro, Elisa; De Luise, Monica; Kurelac, Ivana; Umesh-Ganesh, Nikkitha; Ding, Shujing; Fearnley, Ian M.; Gasparre, Giuseppe; Zeviani, Massimo; Porcelli, Anna Maria; Fernandez-Vizarra, Erika; Iommarini, Luisa. - In: CELL REPORTS. - ISSN 2211-1247. - ELETTRONICO. - 35:3(2021), pp. 109002.1-109002.21. [10.1016/j.celrep.2021.109002]
D’Angelo, Luigi; Astro, Elisa; De Luise, Monica; Kurelac, Ivana; Umesh-Ganesh, Nikkitha; Ding, Shujing; Fearnley, Ian M.; Gasparre, Giuseppe; Zeviani, Massimo; Porcelli, Anna Maria; Fernandez-Vizarra, Erika; Iommarini, Luisa
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/819111
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