Analysis of diverse eukaryotes suggests the existence of an ancestral mitochondrial apparatus derived from the bacterial type II secretion system

Abstract

The type 2 secretion system (T2SS) is present in some Gram-negative eubacteria and used to secrete proteins across the outer membrane. Here we report that certain representative heteroloboseans, jakobids, malawimonads and hemimastigotes unexpectedly possess homologues of core T2SS components. We show that at least some of them are present in mitochondria, and their behaviour in biochemical assays is consistent with the presence of a mitochondrial T2SS-derived system (miT2SS). We additionally identified 23 protein families co-occurring with miT2SS in eukaryotes. Seven of these proteins could be directly linked to the core miT2SS by functional data and/or sequence features, whereas others may represent different parts of a broader functional pathway, possibly also involving the peroxisome. Its distribution in eukaryotes and phylogenetic evidence together indicate that the miT2SS-centred pathway is an ancestral eukaryotic trait. Our findings thus have direct implications for the functional properties of the early mitochondrion.

Bacterial Type II Secretion System and Its Mitochondrial Counterpart

“…The inspection of distant eukaryotic species from the classes Heterolobosea , Jakobida , Malawimonadida , and Hemimastigophora , which are all heterotrophic protists, revealed the unexpected presence of sequences orthologous to the genes encoding core T2SS subunits ( 12 , 13 ). Initial identification of gspG homologues in their genomes led to the thorough analysis directed at the rest of T2SS machinery.…”

“…This strongly suggests that these eukaryotes carry the same ancestral secretion system that was once operating in the LECA. Importantly, several components of miT2SS have been localized to mitochondria, as revealed by immunofluorescence microscopy and proteomics, where they likely assemble into a secretion supercomplex ( 12 ).…”

“…The secretion of proteins by the endosymbiont may have played a crucial role in establishing this interaction that gave rise not only to the mitochondrion and but very likely to the eukaryotic cell itself. Interestingly, genes encoding components of the T2SS pathway have been recently discovered in several eukaryotic lineages, and mitochondrial localization of some of these proteins has been demonstrated ( 12 , 13 ). Phylogenetic distribution of these genes suggests that the T2SS was used by the last eukaryotic common ancestor (LECA) and that therefore its characterization may speak about the early evolutionary history of the eukaryotic cells.…”

Scaffolding Protein GspB/OutB Facilitates Assembly of the Dickeya dadantii Type 2 Secretion System by Anchoring the Outer Membrane Secretin Pore to the Inner Membrane and to the Peptidoglycan Cell Wall

“…The secretins are also shared by the type 3 secretion system (T3SS), type 4 pili (T4P), and the competence and the filamentous phage assembly systems ( 16 – 19 ). Secretin homologs have also been identified in mitochondria of some eukaryotes ( 20 ). Recent cryo-electron microscopy (cryo-EM) structures have revealed important molecular details of the assembly of the megadalton-sized secretin channels consisting of 12 to 16 subunits, with a clear predominance of 15-fold symmetry in more recently acquired near-atomic-resolution structures of the T2SS and T3SS secretins ( 15 , 21 – 28 ).…”

Evidence for an Independent Hydrogenosome-to-Mitosome Transition in the CL3 Lineage of Fornicates

“…While this general scheme is clearly established, its details remain to be worked out. For example, it seems that the mitochondrion of the LECA was more “bacterial” than commonly thought, as continued exploration of mitochondria of diverse protists is expanding the list of presumably ancestral bacterial traits of the organelle preserved in various limited subsets of eukaryotic lineages ( Leger et al, 2015 ; Gray et al, 2020 ; Horváthová et al, 2021 ; Pyrih et al, 2021 ). On the opposite extreme, a number of eukaryote lineages were found to possess mitochondria that are to a varying degree simplified as compared to the textbook model of this organelle (reviewed by Roger et al, 2017 ), yet the list is certainly not complete, as additional mitochondrial variants are continually being reported from diverse corners of the eukaryote phylogeny ( John et al, 2019 ; Lewis et al, 2020 ; Rotterová et al, 2020 ; Yahalomi et al, 2020 ).…”