A Role for Human N-alpha Acetyltransferase 30 (Naa30) in Maintaining Mitochondrial Integrity.
N-terminal acetylation (Nt-acetylation) by N-terminal acetyltransferases (NATs) is one of the most common protein modifications in eukaryotes. The NatC complex represents one of three major NATs of which the substrate profile remains largely unexplored. Here, we defined the in vivo human NatC Nt-acetylome on a proteome-wide scale by combining knockdown of its catalytic subunit Naa30 with positional proteomics. We identified 46 human NatC substrates, expanding our current knowledge on the substrate repertoire of NatC which now includes proteins harboring Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Val, Met-Met, Met-His and Met-Lys N termini. Upon Naa30 depletion the expression levels of several organellar proteins were found reduced, in particular mitochondrial proteins, some of which were found to be NatC substrates. Interestingly, knockdown of Naa30 induced the loss of mitochondrial membrane potential and fragmentation of mitochondria. In conclusion, NatC Nt-acetylates a large variety of proteins and is essential for mitochondrial integrity and function.
From the ‡Medical Biotechnology Center, VIB, B-9000 Ghent, Belgium; petra.vandamme@vib-ugent.be.|§Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
Petra
0000-0001-9090-027X
P
Van Damme
¶Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.
Thomas V
TV
Kalvik
¶Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.|‖Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway.|**Center of Molecular Inflammation Research, Department of Molecular Medicine and Cancer Research, Norwegian University of Technology and Natural Sciences, N-7006 Trondheim, Norway.
Kristian K
KK
Starheim
From the ‡Medical Biotechnology Center, VIB, B-9000 Ghent, Belgium.|§Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
Veronique
V
Jonckheere
¶Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.
Line M
LM
Myklebust
‡‡Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, B-9000 Ghent, Belgium.
Gerben
G
Menschaert
‖Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway.|§§Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway.
Jan Erik
JE
Varhaug
From the ‡Medical Biotechnology Center, VIB, B-9000 Ghent, Belgium.|§Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
Kris
K
Gevaert
¶Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.|§§Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway.
Thomas
T
Arnesen
D000107:Acetylation; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063211:N-Terminal Acetyltransferase C / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D013379:Substrate Specificity
D024101:Mitochondrial Proteins; D063211:N-Terminal Acetyltransferase C; C570950:NAA30 protein, human
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