RSC School Seminar - Professor Megan Maher (University of Melbourne)

Title: The Structural Biology of Complex IV Assembly.

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27 Apr 2023 | 12 - 1pm
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Professor Megan Maher
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Malin Finell
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RSC School Seminar - Megan Maher 27.04.2023

The Structural Biology of Complex IV Assembly.

Abstract

The mitochondrial oxidative phosphorylation (OXPHOS) system generates the bulk of cellular ATP, fuelling the energy demands of most eukaryotes. Five multi-subunit protein complexes in the mitochondrial inner membrane, termed Complexes I to V, comprise the OXPHOS system. Complex IV is the last complex of the electron transport chain, transferring electrons from cytochrome c to molecular oxygen, and in the process, pumping four protons across the inner membrane. In humans, this complex is composed of 14 subunits with the three mtDNA encoded subunits (COX1-3) forming the catalytic core of the enzyme.

Assembly of Complex IV requires the participation of a host of cysteine-rich proteins of the mitochondrial intermembrane space (IMS), which take part in a tightly choreographed series of intermolecular interactions for Complex IV assembly. However, the identities of all proteins involved, their respective roles and the sequence of their participation in Complex IV biogenesis are not known. Crucially, disruptions in this pathway lead to defects in Complex IV assembly, inhibition of oxidative phosphorylation and, in humans, manifests in mitochondrial disease.

This presentation will describe our recent studies of Complex IV assembly factors, which reveal the roles of these proteins in Complex IV assembly and importantly, explain the molecular mechanisms of pathogeneses that occur as a result of identified patient mutations.

Location

Bldg. 32, Lvl. 1, Engineering Lecture