Loss of Rubicon ameliorates doxorubicin-induced cardiotoxicity through enhancement of mitochondrial quality

Liu, Xiaoyun; Zhang, Shasha; An, L.; Wu, Jian; Hu, Xiaowen; Lai, Shuaiwei; Mazhar, Haniya; Zou, Yunzeng; Zhu, Hongxin

doi:10.1016/j.ijcard.2019.07.074

Cited by 22 publications

(11 citation statements)

References 35 publications

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“…Although DOX suppresses autophagic flux chronically, DOX-induced cardiotoxicity is alleviated by inhibition of autophagy initiation in Beclin 1+/-mice [40]. On the other hand, downregulation of Rubicon, a negative regulator of autophagosome-lysosome fusion and endosomal trafficking, also ameliorates DOX-induced cardiotoxicity [41]. These results are consistent with the notion that chronic DOX treatment exacerbates the accumulation of autophagosomes by inhibiting autophagic flux, which in turn induces autophagic cell death in cardiomyocytes and cardiac dysfunction.…”

Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 83%

The role of autophagy in death of cardiomyocytes

Ikeda

Zablocki

Sadoshima

2022

Journal of Molecular and Cellular Cardiology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 83%

The role of autophagy in death of cardiomyocytes

Ikeda

Zablocki

Sadoshima

2022

Journal of Molecular and Cellular Cardiology

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“…A mouse model of doxorubicin-induced cardiotoxicity showed decreased Rubicon expression and mitophagy 16 hours after intraperitoneal injection. Therefore, targeting doxorubicin-induced inhibition of mitophagy, autophagy flux, and mitochondrial dynamics may represent a novel avenue for doxorubicin cardiomyopathy [120].…”

Section: Mitochondrial Quality Controlmentioning

confidence: 99%

Mitophagy, Mitochondrial Dynamics, and Homeostasis in Cardiovascular Aging

Zhang

Ren

2019

Oxidative Medicine and Cellular Longevity

150

113

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Biological aging is an inevitable and independent risk factor for a wide array of chronic diseases including cardiovascular and metabolic diseases. Ample evidence has established a pivotal role for interrupted mitochondrial homeostasis in the onset and development of aging-related cardiovascular anomalies. A number of culprit factors have been suggested in aging-associated mitochondrial anomalies including oxidative stress, lipid toxicity, telomere shortening, metabolic disturbance, and DNA damage, with recent findings revealing a likely role for compromised mitochondrial dynamics and mitochondrial quality control machinery such as autophagy. Mitochondria undergo consistent fusion and fission, which are crucial for mitochondrial homeostasis and energy adaptation. Autophagy, in particular, mitochondria-selective autophagy, namely, mitophagy, refers to a highly conservative cellular process to degrade and clear long-lived or damaged cellular organelles including mitochondria, the function of which gradually deteriorates with increased age. Mitochondrial homeostasis could be achieved through a cascade of independent but closely related processes including fusion, fission, mitophagy, and mitochondrial biogenesis. With improved health care and increased human longevity, the ever-rising aging society has imposed a high cardiovascular disease prevalence. It is thus imperative to understand the role of mitochondrial homeostasis in the regulation of lifespan and healthspan. Targeting mitochondrial homeostasis should offer promising novel therapeutic strategies against aging-related complications, particularly cardiovascular diseases.

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“…Similarly, autophagic flux and mitophagy activity after DOX treatment were improved in Rubicon-deficient hearts. These results suggest that Rubicon deficiency improves DOX-induced cardiotoxicity through enhancement of autophagic flux, which not only prevents excessive accumulation of autophagosomes but also improves cellular quality control mechanisms 7 .…”

Section: Introductionmentioning

confidence: 77%

“…Rubicon may be involved in disease progression through its effects on canonical or noncanonical autophagy (Table 1 ). Recent studies have identified the involvement of Rubicon in heart diseases 7 , 8 . Here, we review the current understanding of Rubicon function in canonical and noncanonical autophagy and summarize the roles of Rubicon in the heart.…”

Section: Introductionmentioning

confidence: 99%

The roles of the inhibitory autophagy regulator Rubicon in the heart: A new therapeutic target to prevent cardiac cell death

2021

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Autophagy contributes to the maintenance of cardiac homeostasis. The level of autophagy is dynamically altered in heart disease. Although autophagy is a promising therapeutic target, only a few selective autophagy activator candidates have been reported thus far. Rubicon is one of the few endogenous negative regulators of autophagy and a potential target for autophagy-inducing therapeutics. Rubicon was initially identified as a component of the Class III PI3K complex, and it has multiple functions, not only in canonical autophagy but also in endosomal trafficking and inflammatory responses. This review summarizes the molecular action of Rubicon in canonical and noncanonical autophagy. We discuss the roles of Rubicon in cardiac stress and the therapeutic potential of Rubicon in cardiac diseases through its modulation of autophagy.

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Loss of Rubicon ameliorates doxorubicin-induced cardiotoxicity through enhancement of mitochondrial quality

Cited by 22 publications

References 35 publications

The role of autophagy in death of cardiomyocytes

The role of autophagy in death of cardiomyocytes

Mitophagy, Mitochondrial Dynamics, and Homeostasis in Cardiovascular Aging

The roles of the inhibitory autophagy regulator Rubicon in the heart: A new therapeutic target to prevent cardiac cell death

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