PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
J Mol Cell Cardiol. Author manuscript; available in PMC 2010 June 1.
Published in final edited form as:
PMCID: PMC2700026
NIHMSID: NIHMS102741

Mitochondria: From Basic Biology to Cardiovascular Disease

This is an exciting time in mitochondrial research. Mitochondria have long been known as the “powerhouse” of the cell and the organelle responsible for generating ATP. In recent years there has been a resurgence of interest in mitochondria as controller of cell death. Mitochondria and metabolism have long been a major focus of the JMCC, the journal of the International Society for Heart Research (ISHR). Indeed the ISHR grew from its roots as the “International Study Group for Research in Cardiac Metabolism”. The JMCC has published many seminal papers on mitochondria and metabolism19. Thus, this Special Issue on mitochondria demonstrates the continuing commitment of the JMCC to this exciting and fundamentally important area of research.

The mitochondrial permeability transition pore (MPT) is usually attributed a key role in regulating cell death. In fact one of the seminal papers showing that inhibition of the MPT could reduce post-ischemic reperfusion injury was published in JMCC by Drs. Griffiths and Halestrap1, who are each authors of review articles in this Special Issue10, 11 (add reference for Griffiths and reference for Halestrap). However as discussed in three focused reviews in this issue, the molecular composition of the MPT is still largely unknown and the topic of intense debate ( 12 and add Reference – Halestrap11, and Di Lisa13). With the recent understanding that mitochondria can modulate cell death has come the realization that alterations in mitochondria are therefore exciting targets of cardioprotection, as discussed in reviews by Brookes14 and Garlid15 and modifiers of disease as discussed by Sack16. Mitochondria, which were originally thought of as static organelles have recently been shown to under go fission and fusion. Whether fission and fusion are active processes in a post mitotic cell such as a cardiomyocyte is a hot topic of debate and is the focus of a review by Sheu17.

Although mitochondria have long been known to be the site of ATP generation, we still do not fully understand how energy needs in the cytosol are signaled to the mitochondria and precisely how mitochondrial oxidative phosphorylation is regulated. This important area is the focus of a review by Balaban18 and several original articles. The review by Balaban18 suggests that Ca2+ and inorganic phosphate (Pi) are key regulators of oxidative phosphorylation. Interestingly these same regulators, Ca and Pi, are key regulators of the MPT13 (ref Di Lisa). Although Ca2+ is recognized as a key regulator of oxidative phosphorylation and is suggested to be an important signal from the cytosol to the mitochondria to activate oxidative phosphorylation, there is considerable debate as to whether Ca2+ transients in the cytosol result in mitochondrial Ca2+ transients or whether the mitochondria integrate the Ca2+ transients. This topic is discussed in a point counterpoint by O’Rouke and Blatter19 and is also discussed in a two review articles10, 20 (Rizzuto and Griffiths) and is the topic of 2 original papers21, 22 (reference Kettleworth and Bers). It is interesting that mitochondria were originally thought to control cytosolic Ca2+ 23, but this hypothesis was later discounted24, 25 because mitochondrial Ca2+ transporter were shown to not be active at cytosolic Ca2+ levels. However, recent work showing the generation of microdomains of high Ca2+ in the proximity of mitochondria has led to a resurgence of the hypothesis that mitochondrial Ca2+ may promptly respond to cytosolic Ca2+ increases and modify their amplitude and diffusion across the cell 26, 27.

It is hoped that this Special Issue on Mitochondria will spur new research and insight into the important role for this organelle in basic biology and its role in cardiovascular disease.

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

References

1. Griffiths EJ, Halestrap AP. Protection by Cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. J Mol Cell Cardiol. 1993;25(12):1461–1469. [PubMed]
2. Murray AJ, Cole MA, Lygate CA, Carr CA, Stuckey DJ, Little SE, Neubauer S, Clarke K. Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart. J Mol Cell Cardiol. 2008;44(4):694–700. [PubMed]
3. Nadtochiy SM, Burwell LS, Brookes PS. Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injury. J Mol Cell Cardiol. 2007;42(4):812–825. [PMC free article] [PubMed]
4. Ignarro LJ. Heart mtNOS, a key mediator of oxidative injury in ischemia/reperfusion. J Mol Cell Cardiol. 2007;43(4):409–410. [PubMed]
5. Boengler K, Gres P, Dodoni G, Konietzka I, Di Lisa F, Heusch G, Schulz R. Mitochondrial respiration and membrane potential after low-flow ischemia are not affected by ischemic preconditioning. J Mol Cell Cardiol. 2007;43(5):610–615. [PubMed]
6. Nishihara M, Miura T, Miki T, Tanno M, Yano T, Naitoh K, Ohori K, Hotta H, Terashima Y, Shimamoto K. Modulation of the mitochondrial permeability transition pore complex in GSK-3beta-mediated myocardial protection. J Mol Cell Cardiol. 2007;43(5):564–570. [PubMed]
7. Sharov VG, Todor A, Khanal S, Imai M, Sabbah HN. Cyclosporine A attenuates mitochondrial permeability transition and improves mitochondrial respiratory function in cardiomyocytes isolated from dogs with heart failure. J Mol Cell Cardiol. 2007;42(1):150–158. [PMC free article] [PubMed]
8. Cohen MV, Philipp S, Krieg T, Cui L, Kuno A, Solodushko V, Downey JM. Preconditioning-mimetics bradykinin and DADLE activate PI3-kinase through divergent pathways. J Mol Cell Cardiol. 2007;42(4):842–851. [PMC free article] [PubMed]
9. Pasdois P, Beauvoit B, Costa AD, Vinassa B, Tariosse L, Bonoron-Adele S, Garlid KD, Dos Santos P. Sarcoplasmic ATP-sensitive potassium channel blocker HMR1098 protects the ischemic heart: implication of calcium, complex I, reactive oxygen species and mitochondrial ATP-sensitive potassium channel. J Mol Cell Cardiol. 2007;42(3):631–642. [PubMed]
10. Griffiths EJ. 2009.
11. Halestrap AP. 2009.
12. Baines CP. The molecular composition of the mitochondrial permeability transition pore. J Mol Cell Cardiol. 2009 [PMC free article] [PubMed]
13. Di Lisa F. 2009.
14. Brookes PS. 2009.
15. Garlid KD, Costa AD, Quinlan CL, Pierre SV, Dos Santos P. Cardioprotective signaling to mitochondria. J Mol Cell Cardiol. 2008 [PMC free article] [PubMed]
16. Sack MN. Type 2 diabetes, mitochondrial biology and the heart. J Mol Cell Cardiol. 2009 [PMC free article] [PubMed]
17. Sheu S-S. 2009.
18. Balaban R. 2009.
19. O’Rourke B, Blatter LA. Mitochondrial Ca(2+) uptake: Tortoise or hare? J Mol Cell Cardiol. 2008 [PMC free article] [PubMed]
20. Rizzuto R. 2009.
21. Kettleworth. 2009.
22. Bers D. 2009.
23. Nicholls DG. The regulation of extramitochondrial free calcium ion concentration by rat liver mitochondria. Biochem J. 1978;176(2):463–474. [PubMed]
24. Somlyo AP, Somlyo AV, Shuman H, Sloane B, Scarpa A. Electron probe analysis of calcium compartments in cryo sections of smooth and striated muscles. Ann N Y Acad Sci. 1978;307:523–544. [PubMed]
25. Brinley FJ, Jr, Tiffert T, Scarpa A. Mitochondria and other calcium buffers of squid axon studied in situ. J Gen Physiol. 1978;72(1):101–127. [PMC free article] [PubMed]
26. Robert V, Gurlini P, Tosello V, Nagai T, Miyawaki A, Di Lisa F, Pozzan T. Beat-to-beat oscillations of mitochondrial [Ca2+] in cardiac cells. EMBO J. 2001;20(17):4998–5007. [PubMed]
27. Rizzuto R, Pozzan T. Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev. 2006;86(1):369–408. [PubMed]