PMID- 18471988
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20211020
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1777
IP  - 7-8
DP  - 2008 Jul-Aug
TI  - Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting 
      mitochondrial respiration.
PG  - 1066-71
LID - 10.1016/j.bbabio.2008.04.023 [doi]
AB  - Cytochrome c (Cyt c) is part of the mitochondrial electron transport chain (ETC), 
      accepting electrons from bc(1) complex and transferring them to cytochrome c 
      oxidase (CcO). The ETC generates the mitochondrial membrane potential, which is 
      used by ATP synthase to produce ATP. In addition, the release of Cyt c from the 
      mitochondria often commits a cell to undergo apoptosis. Considering its central 
      role in life (respiration) and death (apoptosis) decisions one would expect tight 
      regulation of Cyt c function. Reversible phosphorylation is a main cellular 
      regulatory mechanism, but the effect of cell signaling targeting the 
      mitochondrial oxidative phosphorylation system is not well understood, and only a 
      small number of proteins that can be phosphorylated have been identified to date. 
      We have recently shown that Cyt c isolated from cow heart tissue is 
      phosphorylated on tyrosine 97 in vivo, which leads to inhibition of respiration 
      in the reaction with CcO. In this study we isolated Cyt c from a different organ, 
      cow liver, under conditions preserving the physiological phosphorylation state. 
      Western analysis with a phosphotyrosine specific antibody suggested that liver 
      Cyt c is phosphorylated. Surprisingly, the phosphorylation site was unambiguously 
      assigned to Tyr-48 by immobilized metal affinity chromatography/nano-liquid 
      chromatography/electrospray ionization mass spectrometry (IMAC/nano-LC/ESI-MS), 
      and not to the previously identified phospho-Tyr-97 in cow heart. As is true of 
      Tyr-97, Tyr-48 is conserved in eukaryotes. As one possible consequence of Tyr-48 
      phosphorylation we analyzed the in vitro reaction kinetics with isolated cow 
      liver CcO revealing striking differences. Maximal turnover of Tyr-48 
      phosphorylated Cyt c was 3.7 s(-1) whereas dephosphorylation resulted in a 2.2 
      fold increase in activity to 8.2 s(-1). Effects of Tyr-48 phosphorylation based 
      on the Cyt c crystal structure are discussed.
FAU - Yu, Hong
AU  - Yu H
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, 3214 Scott Hall, 540 E. Canfield, Detroit, MI 48201, USA.
FAU - Lee, Icksoo
AU  - Lee I
FAU - Salomon, Arthur R
AU  - Salomon AR
FAU - Yu, Kebing
AU  - Yu K
FAU - Huttemann, Maik
AU  - Huttemann M
LA  - eng
GR  - P20 RR015578/RR/NCRR NIH HHS/United States
GR  - P20 RR015578-076551/RR/NCRR NIH HHS/United States
GR  - P20 RR015578-086804/RR/NCRR NIH HHS/United States
GR  - P20 RR015578-096445/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080422
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Chromatography, Affinity
MH  - Cytochromes c/chemistry/isolation & purification/*metabolism
MH  - Electron Transport Complex IV/chemistry/*metabolism
MH  - Liver/*enzymology
MH  - Models, Molecular
MH  - Oxygen Consumption/*physiology
MH  - Phosphorylation
MH  - Phosphotyrosine/*metabolism
MH  - Tyrosine/metabolism
PMC - PMC2652845
MID - NIHMS90147
EDAT- 2008/05/13 09:00
MHDA- 2008/08/14 09:00
PMCR- 2009/03/09
CRDT- 2008/05/13 09:00
PHST- 2008/01/25 00:00 [received]
PHST- 2008/04/08 00:00 [revised]
PHST- 2008/04/13 00:00 [accepted]
PHST- 2008/05/13 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2008/05/13 09:00 [entrez]
PHST- 2009/03/09 00:00 [pmc-release]
AID - S0005-2728(08)00102-3 [pii]
AID - 10.1016/j.bbabio.2008.04.023 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):1066-71. doi: 
      10.1016/j.bbabio.2008.04.023. Epub 2008 Apr 22.