Evolution and Adaptation of the Mitochondrial Protein Import Machinery in Parasitic Protists: Beyond the Canonical TOM Complex.

The translocase of the outer membrane (TOM) complex is the primary entry gate for nucleus-encoded mitochondrial proteins and is conserved across eukaryotes; however, parasitic protists exhibit remarkable adaptations. This review synthesizes current knowledge on the composition, structure, and function of TOM and related import systems in apicomplexans, kinetoplastids, and anaerobic protists with reduced mitochondrion-related organelles (MROs). We highlight major evolutionary innovations, including the bacterial-origin ATOM complex in trypanosomes-comprising core channel ATOM40, receptors ATOM46/69, structural subunit ATOM19, and multifunctional pATOM36 linking protein import to mitochondrial DNA inheritance-alongside lineage-specific receptors such as Tom60 in Entamoeba histolytica and extreme reductive streamlining in microsporidian mitosomes. Beyond its canonical role in biogenesis, we explore how parasites co-opt the host TOM complex for intracellular survival and how the import machinery integrates with broader cellular processes, including immune signaling, stress responses, and organelle dynamics. Notably, the essential nature of these adapted systems, coupled with their significant divergence from host machinery, highlights their potential as targets for developing novel therapeutic strategies against major parasitic diseases. This work underscores that understanding the diversity of mitochondrial protein import pathways not only provides insights into eukaryotic evolution but may also open new avenues for the development of antiparasitic drugs.