PMID- 9927412
OWN - NLM
STAT- MEDLINE
DCOM- 19990316
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 3
DP  - 1999 Feb 1
TI  - Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial 
      genetic and metabolic stress: a novel mode of inter-organelle crosstalk.
PG  - 522-33
AB  - We have investigated the mechanism of mitochondrial-nuclear crosstalk during 
      cellular stress in mouse C2C12 myocytes. For this purpose, we used cells with 
      reduced mitochondrial DNA (mtDNA) contents by ethidium bromide treatment or 
      myocytes treated with known mitochondrial metabolic inhibitors, including 
      carbonyl cyanide m-chlorophenylhydrazone (CCCP), antimycin, valinomycin and 
      azide. Both genetic and metabolic stresses similarly affected mitochondrial 
      membrane potential (Deltapsim) and electron transport-coupled ATP synthesis, 
      which was also accompanied by an elevated steady-state cytosolic Ca2+ level 
      ([Ca2+]i). The mitochondrial stress resulted in: (i) an enhanced expression of 
      the sarcoplasmic reticular ryanodine receptor-1 (RyR-1), hence potentiating the 
      Ca2+ release in response to its modulator, caffeine; (ii) enhanced levels of 
      Ca2+-responsive factors calineurin, calcineurin-dependent NFATc (cytosolic 
      counterpart of activated T-cell-specific nuclear factor) and c-Jun N-terminal 
      kinase (JNK)-dependent ATF2 (activated transcription factor 2); (iii) reduced 
      levels of transcription factor, NF-kappaB; and (iv) enhanced transcription of 
      cytochrome oxidase Vb (COX Vb) subunit gene. These cellular changes, including 
      the steady-state [Ca2+]i were normalized in genetically reverted cells which 
      contain near-normal mtDNA levels. We propose that the mitochondria-to-nucleus 
      stress signaling occurs through cytosolic [Ca2+]i changes, which are likely to be 
      due to reduced ATP and Ca2+ efflux. Our results indicate that the mitochondrial 
      stress signal affects a variety of cellular processes, in addition to 
      mitochondrial membrane biogenesis.
FAU - Biswas, G
AU  - Biswas G
AD  - Department of Animal Biology, and the Mari Lowe Center for Comparative Oncology, 
      School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 
      19104, USA.
FAU - Adebanjo, O A
AU  - Adebanjo OA
FAU - Freedman, B D
AU  - Freedman BD
FAU - Anandatheerthavarada, H K
AU  - Anandatheerthavarada HK
FAU - Vijayasarathy, C
AU  - Vijayasarathy C
FAU - Zaidi, M
AU  - Zaidi M
FAU - Kotlikoff, M
AU  - Kotlikoff M
FAU - Avadhani, N G
AU  - Avadhani NG
LA  - eng
GR  - R01 AI060921/AI/NIAID NIH HHS/United States
GR  - AG14917-02/AG/NIA NIH HHS/United States
GR  - CA-22762-21/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - 0 (Transcription Factors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Base Sequence
MH  - *Calcium Signaling
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA Primers/genetics
MH  - DNA, Mitochondrial/genetics/metabolism
MH  - Mice
MH  - Mitochondria, Muscle/*metabolism
MH  - Muscle, Skeletal/cytology/*metabolism
MH  - Organelles/metabolism
MH  - Ryanodine Receptor Calcium Release Channel/metabolism
MH  - Stress, Physiological/genetics/metabolism
MH  - Transcription Factors/metabolism
PMC - PMC1171145
EDAT- 1999/02/02 00:00
MHDA- 1999/02/02 00:01
PMCR- 2000/02/01
CRDT- 1999/02/02 00:00
PHST- 1999/02/02 00:00 [pubmed]
PHST- 1999/02/02 00:01 [medline]
PHST- 1999/02/02 00:00 [entrez]
PHST- 2000/02/01 00:00 [pmc-release]
AID - 10.1093/emboj/18.3.522 [doi]
PST - ppublish
SO  - EMBO J. 1999 Feb 1;18(3):522-33. doi: 10.1093/emboj/18.3.522.