# Selective loss of ATP carriers in favour of SLC25A43 orthologues in metamonad mitochondria adapted to anaerobiosis

## TL;DR

This paper explores how anaerobic protists import ATP into their mitochondria using a specific protein, SLC25A43, instead of traditional ATP carriers.

## Contribution

The study identifies SLC25A43 orthologues as ATP-importing carriers in anaerobic metamonad mitochondria, a novel function for this protein.

## Key findings

- Metamonada lack traditional ATP carriers but retain SLC25A43 orthologues.
- SLC25A43 orthologues function as ATP-importing carriers in anaerobic mitochondria.
- These carriers compensate for the loss of ATP production in metamonad mitochondria.

## Abstract

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.