Most cited article - PubMed ID 38060519
Genomics of Preaxostyla Flagellates Illuminates the Path Towards the Loss of Mitochondria
Metamonada is a eukaryotic supergroup of free-living and parasitic anaerobic protists. Their characteristic feature is the presence of highly reduced mitochondria that have lost the ability to produce ATP by oxidative phosphorylation and in some cases even by substrate phosphorylation, with all ATP being imported from the cytosol. Given this striking difference in cellular ATP metabolism when compared to aerobic mitochondria, we studied the presence of mitochondrial carrier proteins (MCPs) mediating the transport of ATP across the inner mitochondrial membrane. Our bioinformatic analyses revealed remarkable reduction of MCP repertoire in Metamonada with striking loss of the major ADP/ATP carrier (AAC). Instead, nearly all species retained carriers orthologous to human SLC25A43 protein, a little-characterized MCP. Heterologous expression of metamonad SLC25A43 carriers confirmed their mitochondrial localization, and functional analysis revealed that SLC25A43 orthologues represent a distinct group of ATP transporters, which we designate as ATP-importing carriers (AIC). Together, our findings suggest that AIC facilitate the ATP import into highly reduced anaerobic mitochondria, compensating for their diminished or absent energy metabolism.
- Keywords
- ADP/ATP carrier, Metamonada, SLC25A43, mitochondrial carrier protein, mitochondrial evolution, mitochondrion-related organelle,
- Publication type
- Journal Article MeSH
Monocercomonoides exilis is a model species of the amitochondrial eukaryotic group Oxymonadida, which makes it a suitable organism for studying the consequences of mitochondrial loss. Although M. exilis has an endobiotic lifestyle, it can be cultured in vitro in polyxenic conditions alongside an uncharacterized prokaryotic community, while attempts to create axenic cultures have not been successful. In this study, we used metagenomic sequencing, transcriptomics, and metabolomics to characterize the microbial consortium that supports the growth of M. exilis. We assembled genomes for 24 bacterial species and identified at least 30 species in total. M. exilis accounted for less than 1.5% of the DNA reads, while bacterial species dominated the sequence data and shifted in abundance over time. Our metabolic reconstruction and differential gene expression analyses show that the bacterial community relies on organic carbon oxidation, fermentation, and hydrogen production, but does not engage in methanogenesis. We observed rapid depletion of amino acids, nucleotides, glyceraldehyde, lactate, fatty acids, and alcohols in the medium, indicating a reliance on external nutrient recycling. The nitrogen cycle in this community is incomplete, with limited nitrogen fixation and no ammonia oxidation. Despite detailed metabolic profiling, we did not find any direct biochemical connections between M. exilis and the prokaryotes. Several bacterial species produce siderophores to assist themselves and others in the community in acquiring iron. However, M. exilis does not appear to benefit directly from siderophore-mediated iron transport and lacks known iron uptake pathways. This indicates that M. exilis may rely indirectly on the iron metabolism of other bacteria through phagocytosis. Additionally, some bacteria synthesize polyamines like spermidine and phosphatidylcholine, which M. exilis may need but cannot produce on its own. As the culture ages, M. exilis shows changes in gene expression consistent with starvation responses, including the upregulation of carbohydrate storage pathways and processes related to exocytosis. These findings provide new insights into microbial interactions within xenic cultures and emphasize the complex nature of maintaining amitochondriate eukaryotes in vitro.
- Publication type
- Journal Article MeSH
Understanding the origin of eukaryotic cells is one of the most difficult problems in all of biology. A key challenge relevant to the question of eukaryogenesis is reconstructing the gene repertoire of the last eukaryotic common ancestor (LECA). As data sets grow, sketching an accurate genomics-informed picture of early eukaryotic cellular complexity requires provision of analytical resources and a commitment to data sharing. Here, we summarise progress towards understanding the biology of LECA and outline a community approach to inferring its wider gene repertoire. Once assembled, a robust LECA gene set will be a useful tool for evaluating alternative hypotheses about the origin of eukaryotes and understanding the evolution of traits in all descendant lineages, with relevance in diverse fields such as cell biology, microbial ecology, biotechnology, agriculture, and medicine. In this Consensus View, we put forth the status quo and an agreed path forward to reconstruct LECA's gene content.
