Characterization of Various Pdss and Coq Proteins in Human Cells and Its Relationship with Mitochondrial Dysfunction or Oxidative Stress

Coenzyme Q (CoQ) is essential for the electron transport chain in the mitochondria. CoQ is primarily present in the form of CoQ10 and CoQ6 in humans and yeast, respectively. Nine Coq proteins (Coq1-Coq9) are required for the CoQ6 biosynthesis in yeast. The human orthologs proteins are COQ proteins, but that of yeast Coq1 is a tetramer containing the PDSS1 and PDSS2 subunits. Several Coq proteins form a multi-subunit protein complex as the main part of the putative“CoQ synthome” in yeast. We have identified specific antibodies and protein forms for most of human PDSS and COQ proteins (except PDSS1, COQ2, and COQ8B), and found that these proteins were present in the mitochondria and present in protein complexes for the first time. Moreover, the decreased levels of some of these proteins caused alterations of protein levels of the other. Our other findings indicate that oxidative stress might increase CoQ10 levels by upregulating PDSS and COQ genes, whereas mitochondrial energy deficiency might decrease CoQ10 levels by suppressing the formation of mature PDSS or COQ proteins in human cells. In the first year, we will find antibodies for those proteins without antibodies, investigate whether PDSS2 or COQ3 has phosphorylated isoform, and elucidate whether these proteins are present in the same protein complexes. In the second year, we will investigate whether the alterations of PDSS or COQ protein levels caused by the decrease of one of the proteins could be associated with changes in the expression of the corresponding genes, examine whether levels of these proteins can be elevated by lipid peroxidation, and study how status of these protein are affected by two conditions of complex V defects. In the third year, we will investigate whether these proteins have direct interaction and whether the protein complexes containing these proteins or the interaction between these proteins could be destabilized in cybrids containing pathogenic mitochondrial mutations. This study will further advance our understanding on these PDSS and COQ proteins and CoQ10 deficiency diseases.

Project ID:PC10907-0927
External Project ID:MOST109-2320-B182-035-MY3