A mitochondrial redox switch licenses the onset of morphogenesis in animals.

Autor: Kahlon U; Department of Biochemistry and Biophysics, University of California, San Francisco, USA.; Touro College of Osteopathic Medicine, Touro University, USA.; These authors have contributed equally., Ricca FD; Department of Biochemistry and Biophysics, University of California, San Francisco, USA.; Dev. & Stem Cell Biology Graduate Program, University of California, San Francisco, USA.; These authors have contributed equally., Pillai SJ; Department of Biochemistry and Biophysics, University of California, San Francisco, USA.; These authors have contributed equally., Olivetta M; Department of Biochemistry, Faculty of Sciences, University of Geneva, Switzerland., Tharp KM; Sanford Burnham Prebys Medical Discovery Institute, San Diego, USA., Jao LE; Department of Cell Biology and Human Anatomy, University of California, Davis, USA., Dudin O; Department of Biochemistry, Faculty of Sciences, University of Geneva, Switzerland., McDonald K; Electron Microscope Lab, University of California, Berkeley, USA., Aydogan MG; Department of Biochemistry and Biophysics, University of California, San Francisco, USA.; Nutrition and Obesity Research Center, University of California, San Francisco, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 29. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1101/2024.10.28.620733
Abstrakt: Embryos undergo pre-gastrulation cleavage cycles to generate a critical cell mass before transitioning to morphogenesis. The molecular underpinnings of this transition have traditionally centered on zygotic chromatin remodeling and genome activation 1,2 , as their repression can prevent downstream processes of differentiation and organogenesis. Despite precedents that oxygen depletion can similarly suspend development in early embryos 3-6 , hinting at a pivotal role for oxygen metabolism in this transition, whether there is a bona fide chemical switch that licenses the onset of morphogenesis remains unknown. Here we discover that a mitochondrial oxidant acts as a metabolic switch to license the onset of animal morphogenesis. Concomitant with the instatement of mitochondrial membrane potential, we found a burst-like accumulation of mitochondrial superoxide (O 2 - ) during fly blastoderm formation. In vivo chemistry experiments revealed that an electron leak from site III Qo at ETC Complex III is responsible for O 2 - production. Importantly, depleting mitochondrial O 2 - fully mimics anoxic conditions and, like anoxia, induces suspended animation prior to morphogenesis, but not after. Specifically, H 2 O 2 , and not ONOO - , NO, or HO•, can single-handedly account for this mtROS-based response. We demonstrate that depleting mitochondrial O 2 - similarly prevents the onset of morphogenetic events in vertebrate embryos and ichthyosporea, close relatives of animals. We postulate that such redox-based metabolic licensing of morphogenesis is an ancient trait of holozoans that couples the availability of oxygen to development, conserved from early-diverging animal relatives to vertebrates.
Competing Interests: Competing interests: Authors declare no competing interests for this study.
Databáze: MEDLINE
Externí odkaz: