8.2. 2023, Bioenergetika

Laboratory name: Bioenergetics

Laboratory website

PhD project: The role of SURF1 protein in biogenesis of mammalian cytochrome c oxidase

Cytochrome c oxidase (COX) is a key enzyme of mitochondrial energetics providing ATP in mammalian cells. COX biogenesis integrates sequential assembly of 14 subunits, encoded by nuclear and mitochondrial genes. It depends on numerous ancillary factors, including SURF1 implicated in insertion of heme a into catalytic subunit COX1. However, its precise role remains unclear, although SURF1 dysfunction causes most frequent COX deficiency - fatal Leigh syndrome. Proposed project will follow up on our studies characterizing COX functional alterations in patients’ fibroblasts harbouring SURF1 mutations, and on key preliminary discovery of incorrect cofactor (heme b) incorporation into COX in mouse SURF1 knock-out. We hypothesize that SURF1 represents an adaptor protein between heme a synthesis enzyme and COX1, that cooperates with putative homologues of assembly factors PET117 and Coa2 described in yeast, thus securing insertion of proper cofactor type. New data characterizing COX biogenesis may contribute to therapy of SURF1-associated neurodegeneration disease.

References:

1.   Kovářová N; Pecina P, Nůsková H, Vrbacký M, Zeviani M, Mráček T, Viscomi C, Houstek J: Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects, BBA 2016, 1862:705-15

2.   Petr Pecina, Erich Gnaiger, JirI Zeman, Ewa Pronicka, Josef Houstek: Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations, Am J Physiol Cell Physiol. 2004 Nov;287(5):C1384-8

Supervisor (email): Mgr. Petr Pecina, Ph.D. (petr.pecina@fgu.cas.cz)

Candidate’s profile (requirements): We are seeking for highly motivated person with MSc. or equivalent degree in cell biology, biochemistry, physiology, or similar field obtained in 2021 or later. Candidate should be fluent in English, enthusiastic for science, curious and with positive mindset. Previous experience with protein purification is an advantage.