Author + information
- Received March 4, 2020
- Revision received April 20, 2020
- Accepted April 20, 2020
- Published online August 24, 2020.
- Jihoon Nah, PhD,
- Daniela Zablocki, MS and
- Junichi Sadoshima, MD, PhD∗ ()
- Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
- ↵∗Address for correspondence:
Dr. Junichi Sadoshima, Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB G609, Newark, New Jersey 07103.
• Autosis is an autophagy-dependent, nonapoptotic, and non-necrotic form of cell death that is characterized by unique morphological and biochemical features, including the presence of ballooning of perinuclear space (PNS) and sensitivity to cardiac glycosides, respectively.
• Autotic cell death may be initiated by excessive accumulation of autophagosomes rather than lysosomal degradation.
• Autosis is stimulated during the late phase of reperfusion after a period of ischemia in the heart when up-regulation of rubicon in the presence of continuous autophagosome production induces massive accumulation of autophagosomes.
• Suppression of autosis, which may reduce death of cardiomyocytes during the late phase of reperfusion, in combination with inhibition of apoptosis and necrosis targeting the early phase of injury, may enhance the effectiveness of treatment for I/R injury in the heart.
Excessive autophagy induces a defined form of cell death called autosis, which is characterized by unique morphological features, including ballooning of perinuclear space and biochemical features, including sensitivity to cardiac glycosides. Autosis is observed during the late phase of reperfusion after a period of ischemia and contributes to myocardial injury. This review discusses unique features of autosis, the involvement of autosis in myocardial injury, and the molecular mechanism of autosis. Because autosis promotes myocardial injury under some conditions, a better understanding of autosis may lead to development of novel interventions to protect the heart against myocardial stress.
This work was supported in part by the U.S. Public Health Service, the American Heart Association, and the Fondation Leducq. Dr. Nah has received support from the American Heart Association (postdoctoral fellowship 18POST34050036). Dr. Sadoshima has received research support from the U.S. Public Health Service (grant AG23039), American Heart Association (award 20 Merit35120374), and Fondation Leducq Transatlantic Network of Excellence (grant 15CBD04). Dr. Zablocki has reported that she has no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 4, 2020.
- Revision received April 20, 2020.
- Accepted April 20, 2020.
- 2020 The Authors