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Cyclophilin D extramitochondrial signaling controls cell cycle progression and chemokine-directed cell motility

Tavecchio, Michele LU ; Lisanti, Sofia; Lam, Aaron; Ghosh, Jagadish C; Martin, Nina M; O'Connell, Michael; Weeraratna, Ashani T.; Kossenkov, Andrew V; Showe, Louise C and Altieri, Dario C (2013) In Journal of Biological Chemistry 288(8). p.61-5553
Abstract

Mitochondria control bioenergetics and cell fate decisions, but how they influence nuclear gene expression is understood poorly. Here, we show that deletion or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl prolyl isomerase and apoptosis regulator, results in increased cell proliferation and enhanced cell migration and invasion. These responses are associated with extensive transcriptional changes, modulation of a chemokine/chemokine receptor gene signature, and activation of the pleiotropic inflammatory mediator, STAT3. In the absence of CypD, active STAT3 enhances cell proliferation via accelerated entry into S-phase and stimulates autocrine/paracrine cell motility through... (More)

Mitochondria control bioenergetics and cell fate decisions, but how they influence nuclear gene expression is understood poorly. Here, we show that deletion or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl prolyl isomerase and apoptosis regulator, results in increased cell proliferation and enhanced cell migration and invasion. These responses are associated with extensive transcriptional changes, modulation of a chemokine/chemokine receptor gene signature, and activation of the pleiotropic inflammatory mediator, STAT3. In the absence of CypD, active STAT3 enhances cell proliferation via accelerated entry into S-phase and stimulates autocrine/paracrine cell motility through Cxcl12-Cxcr4-directed chemotaxis. Therefore, CypD directs mitochondria-to-nuclei inflammatory gene expression in normal and tumor cells. This pathway may contribute to malignant traits under conditions of CypD modulation.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Apoptosis, Cell Cycle, Cell Line, Tumor, Cell Lineage, Cell Movement, Cell Proliferation, Cell Survival, Chemokines, Cyclophilins, Gene Expression Profiling, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Humans, Mice, Mitochondria, NIH 3T3 Cells, RNA, Small Interfering, STAT3 Transcription Factor, Signal Transduction, Journal Article, Research Support, N.I.H., Extramural
in
Journal of Biological Chemistry
volume
288
issue
8
pages
9 pages
publisher
ASBMB
external identifiers
  • scopus:84874326984
ISSN
1083-351X
DOI
10.1074/jbc.M112.433045
language
English
LU publication?
no
id
203b97eb-96fd-4fd8-a31f-dd57ba747ae5
date added to LUP
2017-03-07 09:09:46
date last changed
2018-07-01 04:43:49
@article{203b97eb-96fd-4fd8-a31f-dd57ba747ae5,
  abstract     = {<p>Mitochondria control bioenergetics and cell fate decisions, but how they influence nuclear gene expression is understood poorly. Here, we show that deletion or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl prolyl isomerase and apoptosis regulator, results in increased cell proliferation and enhanced cell migration and invasion. These responses are associated with extensive transcriptional changes, modulation of a chemokine/chemokine receptor gene signature, and activation of the pleiotropic inflammatory mediator, STAT3. In the absence of CypD, active STAT3 enhances cell proliferation via accelerated entry into S-phase and stimulates autocrine/paracrine cell motility through Cxcl12-Cxcr4-directed chemotaxis. Therefore, CypD directs mitochondria-to-nuclei inflammatory gene expression in normal and tumor cells. This pathway may contribute to malignant traits under conditions of CypD modulation.</p>},
  author       = {Tavecchio, Michele and Lisanti, Sofia and Lam, Aaron and Ghosh, Jagadish C and Martin, Nina M and O'Connell, Michael and Weeraratna, Ashani T. and Kossenkov, Andrew V and Showe, Louise C and Altieri, Dario C},
  issn         = {1083-351X},
  keyword      = {Animals,Apoptosis,Cell Cycle,Cell Line, Tumor,Cell Lineage,Cell Movement,Cell Proliferation,Cell Survival,Chemokines,Cyclophilins,Gene Expression Profiling,Gene Expression Regulation,Gene Expression Regulation, Neoplastic,Humans,Mice,Mitochondria,NIH 3T3 Cells,RNA, Small Interfering,STAT3 Transcription Factor,Signal Transduction,Journal Article,Research Support, N.I.H., Extramural},
  language     = {eng},
  month        = {02},
  number       = {8},
  pages        = {61--5553},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Cyclophilin D extramitochondrial signaling controls cell cycle progression and chemokine-directed cell motility},
  url          = {http://dx.doi.org/10.1074/jbc.M112.433045},
  volume       = {288},
  year         = {2013},
}