Conservation of Transit Peptide-Independent Protein Import into the Mitochondrial and Hydrogenosomal Matrix.
The origin of protein import was a key step in the endosymbiotic acquisition of mitochondria. Though the main translocon of the mitochondrial outer membrane, TOM40, is ubiquitous among organelles of mitochondrial ancestry, the transit peptides, or N-terminal targeting sequences (NTSs), recognised by the TOM complex, are not. To better understand the nature of evolutionary conservation in mitochondrial protein import, we investigated the targeting behavior of Trichomonas vaginalis hydrogenosomal proteins in Saccharomyces cerevisiae and vice versa. Hydrogenosomes import yeast mitochondrial proteins even in the absence of their native NTSs, but do not import yeast cytosolic proteins. Conversely, yeast mitochondria import hydrogenosomal proteins with and without their short NTSs. Conservation of an NTS-independent mitochondrial import route from excavates to opisthokonts indicates its presence in the eukaryote common ancestor. Mitochondrial protein import is known to entail electrophoresis of positively charged NTSs across the electrochemical gradient of the inner mitochondrial membrane. Our present findings indicate that mitochondrial transit peptides, which readily arise from random sequences, were initially selected as a signal for charge-dependent protein targeting specifically to the mitochondrial matrix. Evolutionary loss of the electron transport chain in hydrogenosomes and mitosomes lifted the selective constraints that maintain positive charge in NTSs, allowing first the NTS charge, and subsequently the NTS itself, to be lost. This resulted in NTS-independent matrix targeting, which is conserved across the evolutionary divide separating trichomonads and yeast, and which we propose is the ancestral state of mitochondrial protein import.
Institute for Molecular Evolution, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Sriram
S
Garg
Institute for Molecular Evolution, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Jan
J
Stölting
Institute for Molecular Evolution, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Verena
V
Zimorski
Department of Parasitology, Charles University in Prague, Faculty of Science, Czech Republic.
Petr
P
Rada
Department of Parasitology, Charles University in Prague, Faculty of Science, Czech Republic.
Jan
J
Tachezy
Institute for Molecular Evolution, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
William F
WF
Martin
Institute for Molecular Evolution, Heinrich Heine University Düsseldorf, Düsseldorf, Germany gould@hhu.de.
Sven B
SB
Gould
D019143:Evolution, Molecular; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D014246:Trichomonas vaginalis / Q000378:metabolism
D024101:Mitochondrial Proteins; D021382:Protein Sorting Signals; D029701:Saccharomyces cerevisiae Proteins
TOM/TIM; hydrogenosomes; mitochondria; mitosomes; protein import