PMID- 31614941
OWN - NLM
STAT- MEDLINE
DCOM- 20200803
LR  - 20200916
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 8
IP  - 10
DP  - 2019 Oct 13
TI  - The Role of Adenine Nucleotide Translocase in the Assembly of Respiratory 
      Supercomplexes in Cardiac Cells.
LID - 10.3390/cells8101247 [doi]
LID - 1247
AB  - Individual electron transport chain complexes have been shown to assemble into 
      the supramolecular structures known as the respiratory chain supercomplexes 
      (RCS). Several studies reported an associative link between RCS disintegration 
      and human diseases, although the physiological role, structural integrity, and 
      mechanisms of RCS formation remain unknown. Our previous studies suggested that 
      the adenine nucleotide translocase (ANT), the most abundant protein of the inner 
      mitochondrial membrane, can be involved in RCS assembly. In this study, we sought 
      to elucidate whether ANT knockdown (KD) affects RCS formation in H9c2 
      cardiomyoblasts. Results showed that genetic silencing of ANT1, the main ANT 
      isoform in cardiac cells, stimulated proliferation of H9c2 cardiomyoblasts with 
      no effect on cell viability. ANT1 KD reduced the DeltaPsi(m) but increased total 
      cellular ATP levels and stimulated the production of total, but not 
      mitochondrial, reactive oxygen species. Importantly, downregulation of ANT1 had 
      no significant effects on the enzymatic activity of individual ETC complexes 
      I-IV; however, RCS disintegration was stimulated in ANT1 KD cells as evidenced by 
      reduced levels of respirasome, the main RCS. The effects of ANT1 KD to induce RCS 
      disassembly was not associated with acetylation of the exchanger. In conclusion, 
      our study demonstrates that ANT is involved in RCS assembly.
FAU - M Parodi-Rullan, Rebecca
AU  - M Parodi-Rullan R
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, PR 00936-5067, USA. rebecca.parodi-rullan@temple.edu.
FAU - Chapa-Dubocq, Xavier
AU  - Chapa-Dubocq X
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, PR 00936-5067, USA. xavier.chapa@upr.edu.
FAU - Guzman-Hernandez, Roberto
AU  - Guzman-Hernandez R
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, PR 00936-5067, USA. roberto.guzman7@upr.edu.
FAU - Jang, Sehwan
AU  - Jang S
AUID- ORCID: 0000-0003-4426-537X
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, PR 00936-5067, USA. sehwan.jang@upr.edu.
FAU - A Torres-Ramos, Carlos
AU  - A Torres-Ramos C
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, PR 00936-5067, USA. carlos.torres27@upr.edu.
FAU - Ayala-Pena, Sylvette
AU  - Ayala-Pena S
AD  - Department of Pharmacology and Toxicology, School of Medicine, University of 
      Puerto Rico, San Juan, PR 00936-5067, USA. sylvette.ayala@upr.edu.
FAU - Javadov, Sabzali
AU  - Javadov S
AUID- ORCID: 0000-0002-7024-5383
AD  - Department of Physiology, School of Medicine, University of Puerto Rico, San 
      Juan, PR 00936-5067, USA. sabzali.javadov@upr.edu.
LA  - eng
GR  - R25 GM061838/GM/NIGMS NIH HHS/United States
GR  - SC1 GM128210/GM/NIGMS NIH HHS/United States
GR  - SC1 NS095380/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191013
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Reactive Oxygen Species)
RN  - 9068-80-8 (Mitochondrial ADP, ATP Translocases)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Electron Transport/*physiology
MH  - Electron Transport Complex I/metabolism
MH  - Gene Knockdown Techniques/methods
MH  - Male
MH  - Membrane Potential, Mitochondrial/physiology
MH  - Mice
MH  - Mitochondria, Heart/metabolism
MH  - Mitochondrial ADP, ATP Translocases/genetics/*metabolism
MH  - Mitochondrial Membranes/metabolism
MH  - Myocytes, Cardiac/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
PMC - PMC6829619
OTO - NOTNLM
OT  - ETC complexes
OT  - H9c2 cardiomyoblasts
OT  - adenine nucleotide translocase
OT  - mitochondria
OT  - respiratory supercomplexes
COIS- The authors declare no conflict of interest.
EDAT- 2019/10/17 06:00
MHDA- 2020/08/04 06:00
PMCR- 2019/10/01
CRDT- 2019/10/17 06:00
PHST- 2019/06/25 00:00 [received]
PHST- 2019/09/30 00:00 [revised]
PHST- 2019/10/11 00:00 [accepted]
PHST- 2019/10/17 06:00 [entrez]
PHST- 2019/10/17 06:00 [pubmed]
PHST- 2020/08/04 06:00 [medline]
PHST- 2019/10/01 00:00 [pmc-release]
AID - cells8101247 [pii]
AID - cells-08-01247 [pii]
AID - 10.3390/cells8101247 [doi]
PST - epublish
SO  - Cells. 2019 Oct 13;8(10):1247. doi: 10.3390/cells8101247.