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Sarcoplasmic reticulum–mitochondria communication in cardiovascular pathophysiology

  • Review Article
  • Published:

From Nature Reviews Cardiology

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Key Points

  • Sarco/endoplasmic reticulum–mitochondria communication and mitochondrial dynamics are essential regulators of mitochondrial function, cellular metabolism, and calcium homeostasis

  • Sarco/endoplasmic reticulum–mitochondria contacts and mitochondrial dynamics modulate myocardial contractility and vascular smooth muscle cell differentiation

  • Alterations in sarco/endoplasmic reticulum–mitochondria communication and in mitochondrial network morphology are implicated in several cardiovascular pathologies, including heart failure, coronary artery disease, and pulmonary hypertension

  • More studies are required to define the role that alterations in sarco/endoplasmic–mitochondria contacts and mitochondrial dynamics have in the pathogenesis of cardiovascular diseases

Abstract

Repetitive, calcium-mediated contractile activity renders cardiomyocytes critically dependent on a sustained energy supply and adequate calcium buffering, both of which are provided by mitochondria. Moreover, in vascular smooth muscle cells, mitochondrial metabolism modulates cell growth and proliferation, whereas cytosolic calcium levels regulate the arterial vascular tone. Physical and functional communication between mitochondria and sarco/endoplasmic reticulum and balanced mitochondrial dynamics seem to have a critical role for optimal calcium transfer to mitochondria, which is crucial in calcium homeostasis and mitochondrial metabolism in both types of muscle cells. Moreover, mitochondrial dysfunction has been associated with myocardial damage and dysregulation of vascular smooth muscle proliferation. Therefore, sarco/endoplasmic reticulum–mitochondria coupling and mitochondrial dynamics are now viewed as relevant factors in the pathogenesis of cardiac and vascular diseases, including coronary artery disease, heart failure, and pulmonary arterial hypertension. In this Review, we summarize the evidence related to the role of sarco/endoplasmic reticulum–mitochondria communication in cardiac and vascular muscle physiology, with a focus on how perturbations contribute to the pathogenesis of cardiovascular disorders.

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Figure 1: Key components and functions of MAM.
Figure 2: Organelle visualization in the cardiovascular system.
Figure 3: Organelle dynamics and phenotypic changes in the cardiovascular system.

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Acknowledgements

This work was funded by Comision Nacional de Ciencia y Tecnologia (CONICYT), Chile: FONDECYT 1161156 to S.L., FONDECYT 3130749 to C.P., FONDECYT 3160226 to R.B.S., FONDAP 15130011 to M.C., A.F.G.Q., and S.L. C.L.C., C.V.T., and P.E.M. hold CONICYT PhD fellowships. We thank Valentina Parra (University of Chile, Santiago, Chile) for the cardiomyocyte images used in this Review.

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Author notes

  1. Camila Lopez-Crisosto and Christian Pennanen: These authors contributed equally to this work.

Authors and Affiliations

  1. Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas & Facultad de Medicina, Universidad de Chile, Sergio Livingstone 1007, Santiago, 8380492, Chile

    Camila Lopez-Crisosto, Christian Pennanen, Cesar Vasquez-Trincado, Pablo E. Morales, Roberto Bravo-Sagua, Andrew F. G. Quest, Mario Chiong & Sergio Lavandero

  2. Instituto de Nutricion y Tecnologia de los Alimentos (INTA), Universidad de Chile, Avenida El Líbano 5524, Santiago, 7830490, Chile

    Roberto Bravo-Sagua

  3. Centro de Estudios Moleculares de la Celula (CEMC), Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, 8380453, Chile

    Andrew F. G. Quest & Sergio Lavandero

  4. Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, 75235, Texas, USA

    Sergio Lavandero

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  1. Camila Lopez-Crisosto
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  7. Mario Chiong
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  8. Sergio Lavandero
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Corresponding author

Correspondence to Sergio Lavandero.

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Lopez-Crisosto, C., Pennanen, C., Vasquez-Trincado, C. et al. Sarcoplasmic reticulum–mitochondria communication in cardiovascular pathophysiology. Nat Rev Cardiol 14, 342–360 (2017). https://doi.org/10.1038/nrcardio.2017.23

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