PMID- 28986507
OWN - NLM
STAT- MEDLINE
DCOM- 20171117
LR  - 20171217
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 474
IP  - 22
DP  - 2017 Nov 6
TI  - A conserved mammalian mitochondrial isoform of acetyl-CoA carboxylase ACC1 
      provides the malonyl-CoA essential for mitochondrial biogenesis in tandem with 
      ACSF3.
PG  - 3783-3797
LID - 10.1042/BCJ20170416 [doi]
AB  - Mitochondrial fatty acid synthesis (mtFAS) is a highly conserved pathway 
      essential for mitochondrial biogenesis. The mtFAS process is required for 
      mitochondrial respiratory chain assembly and function, synthesis of the lipoic 
      acid cofactor indispensable for the function of several mitochondrial enzyme 
      complexes and essential for embryonic development in mice. Mutations in human 
      mtFAS have been reported to lead to neurodegenerative disease. The source of 
      malonyl-CoA for mtFAS in mammals has remained unclear. We report the 
      identification of a conserved vertebrate mitochondrial isoform of ACC1 expressed 
      from an ACACA transcript splicing variant. A specific knockdown (KD) of the 
      corresponding transcript in mouse cells, or CRISPR/Cas9-mediated inactivation of 
      the putative mitochondrial targeting sequence in human cells, leads to decreased 
      lipoylation and mitochondrial fragmentation. Simultaneous KD of ACSF3, encoding a 
      mitochondrial malonyl-CoA synthetase previously implicated in the mtFAS process, 
      resulted in almost complete ablation of protein lipoylation, indicating that 
      these enzymes have a redundant function in mtFAS. The discovery of a 
      mitochondrial isoform of ACC1 required for lipoic acid synthesis has intriguing 
      consequences for our understanding of mitochondrial disorders, metabolic 
      regulation of mitochondrial biogenesis and cancer.
CI  - (c) 2017 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Monteuuis, Geoffray
AU  - Monteuuis G
FAU - Suomi, Fumi
AU  - Suomi F
FAU - Keratar, Juha M
AU  - Keratar JM
AD  - Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 
      FI-90014, Finland.
FAU - Masud, Ali J
AU  - Masud AJ
AD  - Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 
      FI-90014, Finland.
FAU - Kastaniotis, Alexander J
AU  - Kastaniotis AJ
AD  - Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 
      FI-90014, Finland alexander.kastaniotis@oulu.fi.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171106
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Small Interfering)
RN  - 524-14-1 (Malonyl Coenzyme A)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - EC 6.2.1.- (ACSF3 protein, human)
RN  - EC 6.2.1.- (ACSF3 protein, mouse)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.4.1.2 (ACACA protein, human)
RN  - EC 6.4.1.2 (ACC1 protein, mouse)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
MH  - Acetyl-CoA Carboxylase/genetics/*metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Coenzyme A Ligases/genetics/*metabolism
MH  - Conserved Sequence
MH  - Gene Expression Regulation, Enzymologic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Isoenzymes
MH  - Malonyl Coenzyme A/genetics/*metabolism
MH  - Mice
MH  - Mitochondria/enzymology/*pathology
MH  - RNA, Small Interfering
MH  - Thioctic Acid
OTO - NOTNLM
OT  - ACC1
OT  - ACSF3
OT  - acetyl-CoA carboxylase
OT  - malonyl-CoA
OT  - mitochondrial biogenesis
OT  - mitochondrial fatty acid synthesis
EDAT- 2017/10/08 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/10/08 06:00
PHST- 2017/05/24 00:00 [received]
PHST- 2017/09/29 00:00 [revised]
PHST- 2017/10/03 00:00 [accepted]
PHST- 2017/10/08 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/10/08 06:00 [entrez]
AID - BCJ20170416 [pii]
AID - 10.1042/BCJ20170416 [doi]
PST - epublish
SO  - Biochem J. 2017 Nov 6;474(22):3783-3797. doi: 10.1042/BCJ20170416.