Othonicar 2023 MiPschool Obergurgl

Othonicar Murilo F (2023) Mitochondrial alternative enzymes and supercomplexes: functional and evolutionary insights. MiPschool Obergurgl 2023.

Link: MiPschool Obergurgl 2023

Othonicar Murilo F (2023)

Event: MiPschool Obergurgl 2023

Authors: Othonicar Murilo F, Garcia GS, Oliveira Marcos Tulio

Oxidative phosphorylation (OXPHOS) dysfunction can lead to decreased ATP levels and excessive reactive oxygen species (ROS) formation. Alternative enzymes (AEs) have been successfully used in model organisms to bypass OXPHOS defects and prevent high ROS levels, despite vertebrates and insects having lost their coding genes throughout evolution [1,2,3]. To get a deeper insight into the possible differences between AE-bearing and -lacking animals, we compared the genes coding for subunits of the OXPHOS complexes in tunicates of the genus Ciona with orthologs in Drosophila and humans. We found that Ciona species lack subunits necessary for the formation of respiratory supercomplexes (SCs), which are supramolecular organizations of the invidual OXPHOS complexes able to streamline electron transfer and prevent excessive ROS formation[4]. This suggests that Ciona species do not form SCs, or do so differently. In agreement, we also found that the Ciona intestinalis AE alternative oxidase (AOX), when transgenically expressed in Drosophila melanogaster, preferentially receives electrons from the mitochondrial glycerol-3-phosphate dehydrogenase, which is not known to be involved in SCs. Only when Drosophila SCs appear to be disrupted, AOX is able to receive all electrons from Complex I, a well known SC component. We are currently investigating SC formation in AOX-expressing flies and in C. intestinalis. Our findings could offer valuable insights for optimizing AOX expression in possible future therapeutic settings, and shed light on the evolutionary and functional variations between animal OXPHOS systems.
1. Szibor M, Schenkl C, Barsottini MR, Young L, Moore AL (2022) Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?. Biochemical Journal, 479(12), 1337-1359. https://doi.org/10.1042/BCJ20180192 2. Viscomi C, Moore AL, Zeviani M, Szibor M (2023) Xenotopic expression of alternative oxidase (AOX) to study mechanisms of mitochondrial disease. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1864(2), 148947. https://doi.org/10.1016/j.bbabio.2022.148947 3. Saari S. et al. (2019) Alternative respiratory chain enzymes: Therapeutic potential and possible pitfalls. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1865(4), 854-866.. https://doi.org/10.1016/j.bbadis.2018.10.012 4. Baker N, Patel J, Khacho M (2019) Linking mitochondrial dynamics, cristae remodeling and supercomplex formation: How mitochondrial structure can regulate bioenergetics. Mitochondrion, 49, 259-268. https://doi.org/10.1016/j.mito.2019.06.003

• Keywords: Mitochondria, alternative enzymes, supercomplex, Ciona, Drosophila

• O2k-Network Lab: BR Jaboticabal Oliveira MT

Labels: MiParea: Comparative MiP;environmental MiP 

Organism: Human, Drosophila 

Event: E2 

Affiliation and acknowledgements

Department of Biotechnology, School of Agricultural and Veterinary Sciences, UNESP- São Paulo State University, Jaboticabal, SP, Brazil - murilo.othonicar@unesp.br

Funding: FAPESP(grant 2021/06711-2, 2022/01509-3) and CNPQ(grant 141001/2019-4)