A Single-Mitochondrion Eukaryote Reveals the Principles of Mitochondrial Protein Targeting

Abstract

Mitochondria, which originated from an α-proteobacterial ancestor through endosymbiosis, are not formed de novo within the cell but increase in number exclusively through the division of pre-existing mitochondria. In contrast, the vast majority of mitochondrial proteins are not encoded by mitochondrial DNA but are derived from hundreds of genes encoded in the nuclear genome. Consequently, newly synthesized mitochondrial proteins translated by cytosolic ribosomes are selectively recognized based on peptide sequences appended to their amino termini and are transported into mitochondria through large protein translocase complexes embedded in the mitochondrial membranes. However, the “information” contained within these targeting peptides is cryptic, and the fundamental principles by which mitochondrial protein precursors are selected and discriminated remain incompletely understood. Here, we demonstrate that mitochondrial protein import relies on an unexpectedly simple prerequisite encoded within the targeting presequence. Using the unicellular red alga Cyanidioschyzon merolae, a eukaryote possessing a single mitochondrion, we identified the minimal essential elements required for mitochondrial targeting sequences. Our analyses revealed a remarkably simple rule governing mitochondrial protein recognition and further suggest an evolutionary potential by which novel mitochondrial proteins can arise through minimal sequence changes.