Intracytoplasmic-membrane development in alphaproteobacteria involves the homolog of the mitochondrial crista-developing protein Mic60

[Summary] Mitochondrial cristae expand the surface area of respiratory membranes and ultimately allow for the evolutionary scaling of respiration with cell volume across eukaryotes. The discovery of Mic60 homologs among alphaproteobacteria, the closest extant relatives of mitochondria, suggested that cristae might have evolved from bacterial intracytoplasmic membranes (ICMs). Here, we investigated the predicted structure and function of alphaproteobacterial Mic60, and a protein encoded by an adjacent gene Orf52, in two distantly related purple alphaproteobacteria, Rhodobacter sphaeroides and Rhodopseudomonas palustris. In addition, we assessed the potential physical interactors of Mic60 and Orf52 in R. sphaeroides. We show that the three α helices of mitochondrial Mic60’s mitofilin domain, as well as its adjacent membrane-binding amphipathic helix, are present in alphaproteobacterial Mic60. The disruption of Mic60 and Orf52 caused photoheterotrophic growth defects, which are most severe under low light conditions, and both their disruption and overexpression led to enlarged ICMs in both studied alphaproteobacteria. We also found that alphaproteobacterial Mic60 physically interacts with BamA, the homolog of Sam50, one of the main physical interactors of eukaryotic Mic60. This interaction, responsible for making contact sites at mitochondrial envelopes, has been conserved in modern alphaproteobacteria despite more than a billion years of evolutionary divergence. Our results suggest a role for Mic60 in photosynthetic ICM development and contact site formation at alphaproteobacterial envelopes. Overall, we provide support for the hypothesis that mitochondrial cristae evolved from alphaproteobacterial ICMs and have therefore improved our understanding of the nature of the mitochondrial ancestor.S.A.M.-G. is supported by an EMBO Postdoctoral Fellowship (ALTF 21-2020). M.M.L. was supported by a Nova Scotia Health Research Foundation (NSHRF) Scotia Scholarship 2012-8781. This work was also supported by the Czech Science Foundation grants 20-23513S to H.H. and 19-28778X to M.K., the ERD Fund (003/0000441) to T.B., as well as the Czech Ministry of Education grant OPVVV16_019/0000759 to J.L. and Czech BioImaging grant LM2015062. A.J.R. and J.T.B. were supported by the Natural Sciences and Engineering Research Council of Canada (grants RGPIN-2022-05430 and RGPIN-2018-08398, respectively).Peer reviewe

The Mitochondrial Contact Site and Cristae Organization System and F1FO-ATP Synthase Crosstalk is a Fundamental Property of Mitochondrial Cristae

The acquisition of mitochondria from an endosymbiont closely related to extant alphaproteobacteria occurred prior to the divergence of modern eukaryotes. Since then, diverse eukaryotes have not only developed a number of different mechanisms to adapt to their environment regarding growth and proliferation, but perpetuated certain traits that have persisted for eons. This thesis postulates an ancestral mechanism for cristae development in mitochondria involving interplay between two cristae shaping protein complexes, the Mitochondrial Contact Site and Cristae Organization System and F1FO-ATP Synthase, that has remained conserved throughout eukaryotic diversification for over 2 billion years

Insights into the Evolutionary Conserved Mitochondrial Contact Site and Cristae Organization System in Trypaonsoma brucei Through RNA Interference

This work aims to give insight into the evolution of the mitochondria by investigating novel properties of the evolutionary conserved mitochondrial contact site and cristae organization system complex within the Excavata clade using Trypanosoma brucei as our model. This study shows that this complex indeed contains diverse properties that are not present in the typically studied Opisthokonta clade: e.g. mammalian and yeast organisms