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Regulation of mitochondrial oxidative phosphorylation by tissue-specific isoforms of cytochrome c oxidase

Laboratory name: Bioenergetics

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

PhD project: Regulation of mitochondrial oxidative phosphorylation by tissue-specific isoforms of cytochrome c oxidase

Mitochondrial cytochrome c oxidase (COX) is a key enzyme of oxidative phosphorylation (OXPHOS) system responsible for ATP production in mammalian cells. Expression of tissue-specific isoforms of COX subunits represents a crucial mechanism of OXPHOS regulation. Recently, our studies helped establish the lung isoform of regulatory subunit 4 (COX4I2) as a key component of functionally modified COX with reduced oxygen affinity dedicated to oxygen sensing. Our focus is now expanded to subunit COX6B that occurs either as ubiquitous isoform (COX6B1) or as a protein with exclusive testicular expression (COX6B2). Also, ectopic COX6B2 expression was associated with poor prognosis of lung carcinoma (LC). The project aims to explore the understudied phenomenon of COX6B isoform exchange and its effect on structure and function of OXPHOS. COX6B knock-out/knock-in models will be constructed in HEK293 and LC cell lines to characterize basic functional features of subunit isoforms and their impact on proliferation and tumorigenesis of LC. The role COX6B2 and its post-translational modification will also be studied in the physiological context of sperm maturation and capacitation. The proposed research will provide novel data on OXPHOS biogenesis and regulation and the role of these processes in carcinogenesis and male fertility.

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 2019 or later. Candidate should be fluent in English.

References:

  • Pajuelo Reguera, D., K. Cunatova, M. Vrbacky, A. Pecinova, J. Houstek, T. Mracek and P. Pecina (2020). "Cytochrome c Oxidase Subunit 4 Isoform Exchange Results in Modulation of Oxygen Affinity." Cells 9(2).
  • Čunátová, K., D. Pajuelo Reguera, M. Vrbacký, E. Fernández-Vizarra, S. Ding, I. Fearnley, M. Zeviani, J. Houštěk, T. Mráček and P. Pecina (2021). "Loss of COX4i1 leads to combined respiratory chain deficiency and impaired mitochondrial proteosynthesis." Cells 10(2).