Two Close, Too Close: Sarcoplasmic Reticulum-mitochondrial Crosstalk and Cardiomyocyte Fate

Overview

Journal Circ Res

Specialty Cardiology & Vascular Diseases

Date 2010 Sep 18

PMID 20847324

Citations 37

Authors

Gerald W Dorn 2nd

Luca Scorrano

Affiliations

Soon will be listed here.

Abstract

Mitochondria are key organelles in cell life whose dysfunction is associated with a variety of diseases. Their crucial role in intermediary metabolism and energy conversion makes them a preferred target in tissues, such as the heart, where the energetic demands are very high. In the cardiomyocyte, the spatial organization of mitochondria favors their interaction with the sarcoplasmic reticulum, thereby offering a mechanism for Ca(2+)-mediated crosstalk between these 2 organelles. Recently, the molecular basis for this interaction has begun to be unraveled, and we are learning how endoplasmic reticulum-mitochondrial interactions are often exploited by death signals, such as proapoptotic Bcl-2 family members, to amplify the cell death cascade. Here, we review our present understanding of the structural basis and the functional consequences of the close interaction between sarcoplasmic reticulum and mitochondria on cardiomyocyte function and death.

Citing Articles

Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure.

Latchman N, Stevens T, Bedi K, Prosser B, Margulies K, Elrod J bioRxiv. 2025; .

PMID: 39975328 PMC: 11838275. DOI: 10.1101/2025.01.29.635600.

So close, yet so far away: the relationship between MAM and cardiac disease.

Lu B, Chen X, Ma Y, Gui M, Yao L, Li J Front Cardiovasc Med. 2024; 11():1353533.

PMID: 38374992 PMC: 10875081. DOI: 10.3389/fcvm.2024.1353533.

Enhanced Mitochondria-SR Tethering Triggers Adaptive Cardiac Muscle Remodeling.

Nichtova Z, Fernandez-Sanz C, De la Fuente S, Yuan Y, Hurst S, Lanvermann S Circ Res. 2023; 132(11):e171-e187.

PMID: 37057625 PMC: 10213149. DOI: 10.1161/CIRCRESAHA.122.321833.

Mechanisms of ion selectivity and throughput in the mitochondrial calcium uniporter.

Delgado B, Long S Sci Adv. 2022; 8(50):eade1516.

PMID: 36525497 PMC: 9757755. DOI: 10.1126/sciadv.ade1516.

Disruption of Sarcoplasmic Reticulum-Mitochondrial Contacts Underlies Contractile Dysfunction in Experimental and Human Atrial Fibrillation: A Key Role of Mitofusin 2.

Li J, Qi X, Ramos K, Lanters E, Keijer J, de Groot N J Am Heart Assoc. 2022; 11(19):e024478.

PMID: 36172949 PMC: 9673721. DOI: 10.1161/JAHA.121.024478.

References

Javadov S, Karmazyn M, Escobales N . Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases. J Pharmacol Exp Ther. 2009; 330(3):670-8. DOI: 10.1124/jpet.109.153213. View

Crompton M, Costi A . A heart mitochondrial Ca2(+)-dependent pore of possible relevance to re-perfusion-induced injury. Evidence that ADP facilitates pore interconversion between the closed and open states. Biochem J. 1990; 266(1):33-9. PMC: 1131092. DOI: 10.1042/bj2660033. View

Szabo I, De Pinto V, Zoratti M . The mitochondrial permeability transition pore may comprise VDAC molecules. II. The electrophysiological properties of VDAC are compatible with those of the mitochondrial megachannel. FEBS Lett. 1993; 330(2):206-10. DOI: 10.1016/0014-5793(93)80274-x. View

Andrienko T, Picht E, Bers D . Mitochondrial free calcium regulation during sarcoplasmic reticulum calcium release in rat cardiac myocytes. J Mol Cell Cardiol. 2009; 46(6):1027-36. PMC: 2683203. DOI: 10.1016/j.yjmcc.2009.03.015. View

Martins de Brito O, Scorrano L . Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008; 456(7222):605-10. DOI: 10.1038/nature07534. View

Schmidt A, Wolde M, Thiele C, Fest W, Kratzin H, Podtelejnikov A . Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid. Nature. 1999; 401(6749):133-41. DOI: 10.1038/43613. View

Rothermel B, Hill J . Autophagy in load-induced heart disease. Circ Res. 2008; 103(12):1363-9. PMC: 2607044. DOI: 10.1161/CIRCRESAHA.108.186551. View

Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H . Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature. 2005; 434(7033):652-8. DOI: 10.1038/nature03317. View

Diwan A, Koesters A, Odley A, Pushkaran S, Baines C, Spike B . Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci U S A. 2007; 104(16):6794-9. PMC: 1849960. DOI: 10.1073/pnas.0610666104. View

10.

Mozdy A, McCaffery J, Shaw J . Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol. 2000; 151(2):367-80. PMC: 2192649. DOI: 10.1083/jcb.151.2.367. View

11.

Bellinger A, Mongillo M, Marks A . Stressed out: the skeletal muscle ryanodine receptor as a target of stress. J Clin Invest. 2008; 118(2):445-53. PMC: 2214709. DOI: 10.1172/JCI34006. View

12.

Chen Y, Lewis W, Diwan A, Cheng E, Matkovich S, Dorn 2nd G . Dual autonomous mitochondrial cell death pathways are activated by Nix/BNip3L and induce cardiomyopathy. Proc Natl Acad Sci U S A. 2010; 107(20):9035-42. PMC: 2889094. DOI: 10.1073/pnas.0914013107. View

13.

Frank S, Gaume B, Bergmann-Leitner E, Leitner W, Robert E, Catez F . The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell. 2001; 1(4):515-25. DOI: 10.1016/s1534-5807(01)00055-7. View

14.

James D, Parone P, Mattenberger Y, Martinou J . hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem. 2003; 278(38):36373-9. DOI: 10.1074/jbc.M303758200. View

15.

Wei M, Zong W, Cheng E, LINDSTEN T, Panoutsakopoulou V, Ross A . Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001; 292(5517):727-30. PMC: 3049805. DOI: 10.1126/science.1059108. View

16.

Shen T, Zheng M, Cao C, Chen C, Tang J, Zhang W . Mitofusin-2 is a major determinant of oxidative stress-mediated heart muscle cell apoptosis. J Biol Chem. 2007; 282(32):23354-61. DOI: 10.1074/jbc.M702657200. View

17.

Balaban R . The role of Ca(2+) signaling in the coordination of mitochondrial ATP production with cardiac work. Biochim Biophys Acta. 2009; 1787(11):1334-41. PMC: 3177847. DOI: 10.1016/j.bbabio.2009.05.011. View

18.

Lovell J, Billen L, Bindner S, Shamas-Din A, Fradin C, Leber B . Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. Cell. 2008; 135(6):1074-84. DOI: 10.1016/j.cell.2008.11.010. View

19.

Du H, Guo L, Fang F, Chen D, Sosunov A, McKhann G . Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med. 2008; 14(10):1097-105. PMC: 2789841. DOI: 10.1038/nm.1868. View

20.

Hailey D, Rambold A, Satpute-Krishnan P, Mitra K, Sougrat R, Kim P . Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell. 2010; 141(4):656-67. PMC: 3059894. DOI: 10.1016/j.cell.2010.04.009. View