Next Article in Journal
Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer
Next Article in Special Issue
Novel Techniques Targeting Fibroblasts after Ischemic Heart Injury
Previous Article in Journal
Role of Bioactive Compounds in the Regulation of Mitochondrial Dysfunctions in Brain and Age-Related Neurodegenerative Diseases
Previous Article in Special Issue
Molecular Signaling to Preserve Mitochondrial Integrity against Ischemic Stress in the Heart: Rescue or Remove Mitochondria in Danger
Article

Tfeb-Mediated Transcriptional Regulation of Autophagy Induces Autosis during Ischemia/Reperfusion in the Heart

1
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
2
School of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
3
Cardiovascular Research Institute, Rutgers New Jersey Medical School, 185 South Orange Ave., MSB G609, Newark, NJ 07103, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Antonio Rodríguez-Sinovas
Cells 2022, 11(2), 258; https://doi.org/10.3390/cells11020258
Received: 10 October 2021 / Revised: 2 January 2022 / Accepted: 11 January 2022 / Published: 13 January 2022
(This article belongs to the Special Issue Mechanisms of Ischemic Heart Injury)
Autosis is a unique form of cell death with characteristic morphological and biochemical features caused by dysregulated autophagy. Autosis is observed in the heart during the late phase of ischemia/reperfusion (I/R), when marked accumulation of autophagosomes is induced. We previously showed that the excessive accumulation of autophagosomes promotes autosis in cardiomyocytes. Although the inhibition of autophagic flux via the upregulation of Rubicon induces the accumulation of autophagosomes during I/R, it appears that additional mechanisms exacerbating autophagosome accumulation are required for the induction of autosis. Here, we show that Tfeb contributes to the induction of autosis during the late phase of I/R in the heart. During myocardial reperfusion, Tfeb is activated and translocated into the nucleus, which in turn upregulates genes involved in autophagy and lysosomal function. The overexpression of Tfeb enhanced cardiomyocyte death induced by a high dose of TAT-Beclin 1, an effect that was inhibited by the downregulation of Atg7. Conversely, the knockdown of Tfeb attenuated high-dose TAT-Beclin1-induced death in cardiomyocytes. Although the downregulation of Tfeb in the heart significantly decreased the number of autophagic vacuoles and inhibited autosis during I/R, the activation of Tfeb activity via 3,4-dimethoxychalcone, an activator of Tfeb, aggravated myocardial injury during I/R. These findings suggest that Tfeb promotes cardiomyocyte autosis during the late phase of reperfusion in the heart. View Full-Text
Keywords: autophagic cell death; autosis; Tfeb; ischemia/reperfusion autophagic cell death; autosis; Tfeb; ischemia/reperfusion
Show Figures

Figure 1

MDPI and ACS Style

Nah, J.; Sung, E.-A.; Zhai, P.; Zablocki, D.; Sadoshima, J. Tfeb-Mediated Transcriptional Regulation of Autophagy Induces Autosis during Ischemia/Reperfusion in the Heart. Cells 2022, 11, 258. https://doi.org/10.3390/cells11020258

AMA Style

Nah J, Sung E-A, Zhai P, Zablocki D, Sadoshima J. Tfeb-Mediated Transcriptional Regulation of Autophagy Induces Autosis during Ischemia/Reperfusion in the Heart. Cells. 2022; 11(2):258. https://doi.org/10.3390/cells11020258

Chicago/Turabian Style

Nah, Jihoon, Eun-Ah Sung, Peiyong Zhai, Daniela Zablocki, and Junichi Sadoshima. 2022. "Tfeb-Mediated Transcriptional Regulation of Autophagy Induces Autosis during Ischemia/Reperfusion in the Heart" Cells 11, no. 2: 258. https://doi.org/10.3390/cells11020258

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop