Mitochondrial protein assemblies: Biogenesis of the cytochrome c oxidase and mitophagic signaling complexes

von Mariia Levchenko
Dissertation
Datum der mündl. Prüfung:2015-12-02
Erschienen:2016-09-05
Betreuer:Prof. Dr. Peter Rehling
Gutachter:Prof. Dr. Peter Rehling
Gutachter:Prof. Dr. Blanche Schwappach
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-5841

 

 

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Name:PhD thesis Mariia Levchenko.pdf
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Description:PhD thesis

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Englisch

Mitochondrial physiology requires a constant balance between biosynthesis and degradation events. This thesis addresses both mitochondrial biogenesis, exemplified by cytochrome c oxidase assembly, and mitochondrial removal in the course of mitophagy. The cytochrome c oxidase is the terminal enzyme of the respiratory chain. It assembles in a complicated pathway from nuclear- and mitochondria-encoded subunits. Together with other respiratory chain complexes the cytochrome c oxidase is included into supercomplexes. These oligomeric structures are implicated in efficient electron transfer and increased stability of their constituents. The first aim of this thesis was to address the role of an uncharacterized protein Cox26 in supercomplex biogenesis. I have identified Cox26 as a novel cytochrome c oxidase subunit that associates with respiratory chain supercomplexes. I discovered that Cox26 is required for efficient formation of supercomplexes and cytochrome c oxidase. Cox26 is expendable for catalytic activity of individual respiratory complexes and mitochondrial respiration. Abnormal biogenesis of the respiratory chain compromises cellular energy metabolism and leads to mitochondrial damage. Defective mitochondria have to be selectively removed in the course of mitophagy. Mitophagy receptors on mitochondrial surface provide the basis for such selectivity. Thus, the second goal of my project was to understand how yeast mitophagy receptor Atg32 governs mitochondrial recognition by the mitophagic machinery. I found that Atg32 is included into a mitochondrial complex, which dissociates during mitophagy. Atg32 is subsequently modified and delivered to the vacuole, presumably together with its cargo. Unaltered receptor is digested by an undetermined protease, possibly preventing excessive mitochondrial degradation.
Keywords: mitochondria; mitophagy; Atg32; Cox26; mitochondrial degradation; mitochondrial quality control; cytochrome c oxidase; supercomplexes; respiration; COX assembly
 
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