Structural and Functional Consequences of C-n-ras Constitutively Associated with Intact Mitochondria.
From: Department of Cell Biology, NC10, Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH 44195, USA. wolfmaa@ccf.org
Biochimica et biophysica acta
- Publish Date: Oct 2006
- ISSN: 0006-3002
- Volume: 1763
- Issue: 10
- Pages: 1108-24
- Medium: Print
- Language: English
- Citation (JAMA): Wolfman Janice C, Planchon Sarah M, Liao Jinhui, et al. Structural and Functional Consequences of C-n-ras Constitutively Associated with Intact Mitochondria.. Biochim. Biophys. Acta Oct 2006;1763:1108-24
Abstract
We demonstrate that both c-N-Ras and c-K(B)-Ras are constitutively associated with purified mitochondria. c-K(B)-Ras is associated with the mitochondrial outer membrane, and c-N-Ras is associated with both the outer membrane and inner mitochondrial compartments. The mitochondrial morphology is abnormal in both c-N-Ras negative and K-Ras negative cells. Normal mitochondrial morphology was restored by targeting N-Ras to both the inner and outer mitochondrial compartments, or by ectopically expressing c-K(B)-Ras. Impaired mitochondrial function can result in increased CHOP and NFkappaB activity, typical for a retrograde signaling response. Both are constitutively elevated in the N-Ras negative cells, but not in the K-Ras negative background, and are restored by c-N-Ras targeted exclusively to the inner mitochondrial compartment. Surprisingly, both targeting and the ability to functionally reduce retrograde transcriptional activity were found to be independent of c-N-Ras farnesylation. Overall, these data demonstrate for the first time a (1) farnesylation independent function for c-N-Ras and (2) that N-Ras within the inner mitochondrial compartment is an essential component of the retrograde signaling system between the mitochondria and nucleus.
Mesh Headings (Keywords): Animals, Cells, Cultured, Mice, Mitochondria, Mitochondrial Membranes, Protein Isoforms, ras Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16996152
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.