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Autophagic Regulation of Cardiomyocyte Survival and Heart Regeneration

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Autophagy in Health and Disease

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Autophagy is regarded as an essential cellular protective mechanism of cardiomyocytes against a panel of stresses such as myocardial infarction and ischemia–reperfusion. Autophagy-dependent protection against such stresses is especially important in cardiomyocytes, since adult cardiomyocytes are terminally differentiated cells and considered not to proliferate any more. However, this concept of adult cardiomyocyte nonproliferation has recently been challenged by many studies. Although the presence of cardiac stem cells in adult heart remains a subject of debate, there is ample evidence for the presence of cardiac progenitor cells that can differentiate into several heart-resident cells. Furthermore, adult cardiomyocytes can reenter the cell cycle and proliferate upon activation of YAP, a transcriptional coactivator downstream of the hippo pathway. In addition, cardiac cells in the epicardium can also transform into cardiofibroblasts, which contribute to tissue regeneration by filling damaged parts of tissue with themselves as well as extracellular matrix. This process seems to be executed through epithelial–mesenchymal transition (EMT). Autophagy has been supposed to participate in the maintenance of cardiomyocyte homeostasis not only by protecting the cells against stress, but also by facilitating regeneration. In this chapter, we discuss the possible roles of autophagy in protection as well as the promotion of regeneration of cardiomyocytes by regulating the hippo/YAP pathway and EMT.

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Abbreviations

8-OHdG:

8-Oxo-2′-deoxyguanosine

Atg:

Autophagy-related

BH:

Bcl-2 homologous

CMA:

Chaperone-mediated autophagy

CTGF:

Connective tissue growth factor

EMT:

Epithelial–mesenchymal transition

FIP200:

Focal adhesion kinase family interacting protein of 200 kDa

LAMP:

Lysosome-associated membrane protein

LATS:

Large tumor suppressor homolog

LC3:

Microtubles-associated protein light chain3

MET:

Mesenchymal–epithelial transition

Mst:

Mammalian STE20-like protein kinase

RASSF1:

Ras association domain-containing protein 1

ROS:

Reactive oxygen species

Sav:

Salvador homolog

TAZ:

Transcriptional coactivator with PDZ-binding motif

TEAD:

Transcriptiona enhancer-associated domain

ULK:

Unc-51-like kinase

YAP:

Yes-associated protein

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Acknowledgments

This work was supported in part by MEXT KAKENHI Grant Number JP25460862. The authors declare no conflicts of interest.

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  1. Department of Forensic Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Toshihiko Aki, Kanako Noritake, Kana Unuma & Koichi Uemura

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  1. Toshihiko Aki
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Correspondence to Toshihiko Aki .

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  1. Ottawa, ON, Canada

    Kursad Turksen

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Aki, T., Noritake, K., Unuma, K., Uemura, K. (2018). Autophagic Regulation of Cardiomyocyte Survival and Heart Regeneration. In: Turksen, K. (eds) Autophagy in Health and Disease. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-98146-8_7

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