Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies DOI Creative Commons
Wei Ma, Yingying Lü, Xin Jin

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: 65, P. 297 - 327

Published: May 14, 2024

Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules organelles degradation, a termed selective autophagy. Recently, accumulating studies have demonstrated that abnormality of closely associated with occurrence progression many human diseases, including neurodegenerative cancers, metabolic cardiovascular diseases. This review aims at systematically comprehensively introducing its role various while unravelling molecular mechanisms By providing theoretical basis development related small-molecule drugs as well treating this seeks to contribute understanding therapeutic potential. review, we introduce dissect major categories been discovered. We also focus recent advances underlying both classical non-classical Moreover, current situation targeting different types further summarized, valuable insights into discovery more candidate future. On other hand, reveal clinically relevant implementations are potentially autophagy, such predictive approaches treatments tailored individual patients.

Language: Английский

Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases DOI
Jun Ren, Yaguang Bi, James R. Sowers

et al.

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 18(7), P. 499 - 521

Published: Feb. 22, 2021

Language: Английский

Citations

491
Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications DOI
Jun Ren, Ne N. Wu, Shuyi Wang

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1745 - 1807

Published: May 5, 2021

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to rapidly increased overweight obesity. To this point, epidemiological, clinical, experimental evidence supports existence unique disease entity termed "obesity cardiomyopathy," which develops independent hypertension, coronary disease, other diseases. Our contemporary review evaluates for pathological condition, examines putative responsible mechanisms, discusses therapeutic options disorder. Clinical findings have consolidated presence left ventricular dysfunction Experimental investigations uncovered pathophysiological changes myocardial structure function genetically predisposed diet-induced Indeed, consolidates wide array cellular molecular mechanisms underlying etiology obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover free fatty acids, lipotoxicity, amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, fibrosis, dampened flow reserve, microvascular (microangiopathy), endothelial impairment. Given important role risk failure, that with preserved systolic recent rises COVID-19-associated cardiovascular mortality, should provide compelling cardiomyopathy, various comorbid conditions, offer new insights into potential approaches (pharmacological lifestyle modification) clinical management cardiomyopathy.

Language: Английский

Citations

253
Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics DOI Creative Commons
Amir Ajoolabady,

Shuyi Wang,

Guido Kroemer

et al.

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 225, P. 107848 - 107848

Published: April 4, 2021

Language: Английский

Citations

217
Mitophagy in cardiovascular diseases: molecular mechanisms, pathogenesis, and treatment DOI Creative Commons
Amir Ajoolabady, Mario Chiong, Sergio Lavandero

et al.

Trends in Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(10), P. 836 - 849

Published: July 22, 2022

Language: Английский

Citations

126
FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis DOI

Zhaohui Pei,

Yandong Liu, Suqin Liu

et al.

Metabolism, Journal Year: 2021, Volume and Issue: 122, P. 154840 - 154840

Published: July 29, 2021

Language: Английский

Citations

117
The multifaceted regulation of mitophagy by endogenous metabolites DOI Open Access
Ting Zhang, Qian Liu, Weihua Gao

et al.

Autophagy, Journal Year: 2021, Volume and Issue: 18(6), P. 1216 - 1239

Published: Sept. 29, 2021

Owing to the dominant functions of mitochondria in multiple cellular metabolisms and distinct types regulated cell death, maintaining a functional mitochondrial network is fundamental for homeostasis body fitness response physiological adaptations stressed conditions. The process mitophagy, which dysfunctional or superfluous are selectively engulfed by autophagosome subsequently degraded lysosome, has been well formulated as one major mechanisms quality control. To date, PINK1-PRKN-dependent receptors (including proteins lipids)-dependent pathways have characterized determine mitophagy mammalian cells. highly responsive dynamics endogenous metabolites, including iron-, calcium-, glycolysis-TCA-, NAD+-, amino acids-, fatty cAMP-associated metabolites. Herein, we summarize recent advances toward molecular details regulation We also highlight key regulations shed new light on bidirectional interplay between metabolisms, with attempting provide perspective insight into nutritional intervention metabolic disorders deficit.

Language: Английский

Citations

114
Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis DOI Creative Commons
Lei Liu, Yanjun Li, Guo Chen

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: Oct. 12, 2023

Mitochondrial mass and quality are tightly regulated by two essential opposing mechanisms, mitochondrial biogenesis (mitobiogenesis) mitophagy, in response to cellular energy needs other environmental cues. Great strides have been made uncover key regulators of these complex processes. Emerging evidence has shown that there exists a tight coordination between mitophagy mitobiogenesis, their defects may cause many human diseases. In this review, we will first summarize the recent advances discovery molecular regulations mitobiogenesis then focus on mechanism signaling pathways involved simultaneous regulation tissue or cultured cells needs, stress, pathophysiological conditions. Further studies crosstalk processes at level provide better understanding how cell maintains optimal fitness function under physiological conditions, which holds promise for fighting aging aging-related

Language: Английский

Citations

86
FUNDC1 interacts with GPx4 to govern hepatic ferroptosis and fibrotic injury through a mitophagy-dependent manner DOI Creative Commons
Yaguang Bi,

Shuolin Liu,

Xing Qin

et al.

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 55, P. 45 - 60

Published: Feb. 23, 2023

Liver fibrosis is a life-threatening pathological anomaly which usually evolves into advanced liver cirrhosis and hepatocellular carcinoma although limited therapeutic option readily available. FUN14 domain containing 1 (FUNDC1) mitophagy receptor with little information in fibrosis. This study was designed to examine the role for FUNDC1 carbon tetrachloride (CCl4)-induced injury. GEO database analysis subsequent validation of biological processes including western blot, immunofluorescence, co-immunoprecipitation were applied clarify regulatory on ferroptosis. Our data revealed elevated levels tissues patients fibrotic injury CCl4-challenged mice. deletion protected against CCl4-induced hepatic anomalies Moreover, ameliorated ferroptosis vivo vitro. Mechanically, interacted glutathione peroxidase (GPx4), selenoenzyme neutralize lipid hydroperoxides ferroptosis, via its 96–133 amino acid facilitate GPx4 recruitment mitochondria from cytoplasm. entered through mitochondrial protein import system-the translocase outer membrane/translocase inner membrane (TOM/TIM) complex, prior degradation mainly along ROS-induced damaged mitochondria, resulting hepatocyte Taken together, our favored that promoted binding translocation TOM/TIM where degraded by trigger Targeting may be promising approach

Language: Английский

Citations

81
FUNDC1 protects against doxorubicin-induced cardiomyocyte PANoptosis through stabilizing mtDNA via interaction with TUFM DOI Creative Commons
Yaguang Bi, Haixia Xu, Xiang Wang

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(12)

Published: Dec. 5, 2022

Abstract Doxorubicin (DOX) is an effective anthracycline chemotherapeutic anticancer drug with its life-threatening cardiotoxicity severely limiting clinical application. Mitochondrial damage-induced cardiomyocyte death considered essential cue for DOX cardiotoxicity. FUN14 domain containing 1 (FUNDC1) a mitochondrial membrane protein participating in the regulation of integrity multiple diseases although role cardiomyopathy remains elusive. Here, we examined whether PANoptosis, novel type programmed cell closely associated damage, was involved DOX-induced heart injury, and FUNDC1-mediated if any. FUNDC1 downregulated tissues patients dilated (DCM) DOX-challenged mice. deficiency aggravated cardiac dysfunction, PANoptosis. Further examination revealed that countered cytoplasmic release DNA (mtDNA) activation PANoptosome through interaction Tu translation elongation factor (TUFM), key translational expression repair DNA, via 96–133 amino acid domain. TUFM intervention reversed FUNDC1-elicited protection against mtDNA cytosolic Our findings shed light toward beneficial thus offering therapeutic promises

Language: Английский

Citations

75
PANoptosis: Mechanisms, biology, and role in disease DOI Open Access

Xu Sun,

Yanpeng Yang,

Xiaona Meng

et al.

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 246 - 262

Published: Oct. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Language: Английский

Citations

72