The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Mitofusin 2-Containing Mitochondrial-Reticular Microdomains Direct Rapid Cardiomyocyte Bioenergetic Responses Via Interorganelle Ca 2+ Crosstalk
Open accessAbstract
Rationale: Mitochondrial Ca 2+ uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association of mitochondria to the sarcoplasmic reticulum (SR) may explain efficient mitochondrial Ca 2+ uptake despite low Ca 2+ affinity of the mitochondrial Ca 2+ uniporter. However, the existence of such mitochondrial Ca 2+ microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic reticulum to mitochondria in noncardiac cells. Objective: To elucidate roles for Mfn1 and 2 in SR-mitochondrial tethering, Ca 2+ signaling, and bioenergetic regulation in cardiac myocytes. Methods and Results: Fruit fly heart tubes deficient of the Drosophila Mfn ortholog MARF had increased contraction-associated and caffeine-sensitive Ca 2+ release, suggesting a role for Mfn in SR Ca 2+ handling. Whereas cardiac-specific Mfn1 ablation had no effects on murine heart function or Ca 2+ cycling, Mfn2 deficiency decreased cardiomyocyte SR-mitochondrial contact length by 30% and reduced the content of SR-associated proteins in mitochondria-associated membranes. This was associated with decreased mitochondrial Ca 2+ uptake (despite unchanged mitochondrial membrane potential) but increased steady-state and caffeine-induced SR Ca 2+ release. Accordingly, Ca 2+ -induced stimulation of Krebs cycle dehydrogenases during β-adrenergic stimulation was hampered in Mfn2-KO but not Mfn1-KO myocytes, evidenced by oxidation of the redox states of NAD(P)H/NAD(P) + and FADH 2 /FAD. Conclusions: Physical tethering of SR and mitochondria via Mfn2 is essential for normal interorganelle Ca 2+ signaling in the myocardium, consistent with a requirement for SR-mitochondrial Ca 2+ signaling through microdomains in the cardiomyocyte bioenergetic feedback response to physiological stress.
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Mitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280
Self-citationClose Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca 2+ Responses
Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., & Pozzan, T. (1998) · Science · doi:10.1126/science.280.5370.1763 · Cited by 2,257
Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction
Chen, H., Chomyn, A., & Chan, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503062200 · Cited by 1,376
Mitochondrial fusion protects against neurodegeneration in the cerebellum
Chen, H., McCaffery, J. M., & Chan, D. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.026 · Cited by 924
Cited by
The cell biology of mitochondrial membrane dynamics
Giacomello, M., Pyakurel, A., Glytsou, C., & Scorrano, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0210-7 · Cited by 1,550
PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria
Chen, Y., & Dorn, G. W. (2013) · Science · doi:10.1126/science.1231031 · Cited by 1,323
Self-citationMitochondrial dynamics in adaptive and maladaptive cellular stress responses
Eisner, V., Picard, M., & Hajnóczky, G. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0133-0 · Cited by 622
Endoplasmic reticulum-mitochondrial contactology: structure and signaling functions
Csordás, G., Weaver, D., & Hajnóczky, G. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.009 · Cited by 625
Self-citationImbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice
Wai, T., García-Prieto, J., Baker, M. J., Merkwirth, C., Benit, P., Rustin, P., Rupérez, F. J., Barbas, C., Ibañez, B., & Langer, T. (2015) · Science · doi:10.1126/science.aad0116 · Cited by 551
Metadata
- Authors
- Chen, Y., Csordás, G., Jowdy, C., Schneider, T. G., Csordás, N., Wang, W., Liu, Y., Kohlhaas, M., Meiser, M., Bergem, S., Nerbonne, J. M., Dorn, G. W., & Maack, C.
- Venue
- Circulation Research
- Published
- 2012-09-14
- Volume
- 111
- Issue
- 7
- Pages
- 863-875
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2158725951
- Cited by
- 348
- References
- 6
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chen, Y., Csordás, G., Jowdy, C., Schneider, T. G., Csordás, N., Wang, W., Liu, Y., Kohlhaas, M., Meiser, M., Bergem, S., Nerbonne, J. M., Dorn, G. W., & Maack, C. (2012). Mitofusin 2-Containing Mitochondrial-Reticular Microdomains Direct Rapid Cardiomyocyte Bioenergetic Responses Via Interorganelle Ca 2+ Crosstalk. Circulation Research. https://doi.org/10.1161/circresaha.112.266585
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