Review
Biochemistry & Molecular Biology
Jing Liu, Lijuan Wang, Hua He, Yueying Liu, Yiqun Jiang, Jinfeng Yang
Summary: Chaperone-mediated autophagy (CMA) is a process that degrades proteins labeled with KFERQ-like motifs within cells to terminate their functioning. CMA plays a crucial role in cell proliferation and apoptosis. Its relationship with cancer is complex, with contradictory effects in cancer cells and untransformed cells, leading to interest in regulating CMA activity for cancer therapy.
Article
Biochemistry & Molecular Biology
Jinyun Chen, Yujie Yang, Wade A. Russu, William K. Chan
Summary: The study reports that AHR undergoes chaperone-mediated autophagy in MDA-MB-468 triple-negative breast cancer cells, with specific characteristics and regulatory mechanisms involved in the degradation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Virginie Hubert, Sebastian Weiss, Andrew Jackson Rees, Renate Kain
Summary: Autophagy is a central mechanism for maintaining cellular homeostasis. Chaperone-mediated autophagy (CMA) is a selective degradation pathway for soluble cytosolic proteins. Altered levels of CMA are associated with various diseases, but its therapeutic potential is still limited.
Article
Environmental Sciences
Shali Yu, Zhijie Li, Qin Zhang, Rui Wang, Zixuan Zhao, Wenjie Ding, Fengxu Wang, Chuan Sun, Juan Tang, Xiaoke Wang, Hongbing Zhang, Rongrong Huang, Qiyun Wu, Junkang Jiang, Xinyuan Zhao
Summary: This study reveals a novel mechanism by which antimony (Sb) triggers neurotoxicity through inducing ferroptosis in neurons by limiting the degradation of the antioxidant glutathione peroxidase 4 (GPX4). The study also found that inhibition of chaperone-mediated autophagy (CMA) can attenuate Sb-induced GPX4 degradation. These findings provide new insights into the understanding of Sb-induced neurotoxicity.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Editorial Material
Cell Biology
S. Joseph Endicott, Richard A. Miller
Summary: PTEN is a negative regulator of the INS-PI3K-AKT pathway and plays a critical role in metabolism and cell growth. It is frequently mutated in cancer, but overexpression of PTEN extends lifespan in mice. Our recent study demonstrated that PTEN activates chaperone-mediated autophagy (CMA) and selectively degrades metabolic enzymes to suppress glycolysis and fatty acid synthesis. This suggests that PTEN-mediated CMA activation could modulate health and metabolism.
Article
Multidisciplinary Sciences
Thomas G. Martin, Valerie D. Myers, Praveen Dubey, Shubham Dubey, Edith Perez, Christine S. Moravec, Monte S. Willis, Arthur M. Feldman, Jonathan A. Kirk
Summary: The authors demonstrate that decreased expression of BAG3 in the heart leads to reduced sarcomere protein turnover, impacting mechanical function, and that sarcomere force-generating capacity can be restored through BAG3 gene therapy.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Enrico Desideri, Serena Castelli, Coralie Dorard, Stefanie Toifl, Gian Luca Grazi, Maria Rosa Ciriolo, Manuela Baccarini
Summary: This study demonstrates that chaperone-mediated autophagy (CMA) can degrade two proteins, YAP1 and IL6ST, in liver cancer, thereby suppressing tumor growth. Additionally, downregulation of LAMP2A promotes proliferation and migration in liver cancer cells in a YAP1 and IL6ST-dependent manner.
Article
Oncology
Fan Yang, Rui Sun, Zeng Hou, Fang-Lin Zhang, Yi Xiao, Yun-Song Yang, Shao-Ying Yang, Yi-Fan Xie, Ying-Ying Liu, Cheng Luo, Guang-Yu Liu, Zhi-Min Shao, Da-Qiang Li
Summary: In this study, it is found that HSP90 N-terminal inhibitors can disrupt MORC2 homodimer formation and promote its lysosomal degradation, thereby reducing the stability of MORC2 in cancer cells. This provides a new possibility for the treatment of MORC2-overexpressing tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Katherine K. Zhang, Peichuan Zhang, Anagha Kodur, Ilkim Erturk, Calvin M. Burns, Cynthia Kenyon, Richard A. Miller, S. Joseph Endicott
Summary: Chaperone-mediated autophagy (CMA) selectively degrades crucial proteins for glycolysis, fatty acid metabolism, and age-associated diseases. Previous studies suggested a decline in CMA with age due to decreased levels of LAMP2A, the main component of the CMA complex. However, a recent study on genetically heterogeneous mice found no age-related changes in LAMP2A levels or CMA activity, except for sex differences.
Article
Neurosciences
Hua Zhang, Caitlynn Knight, S. R. Wayne Chen, Ilya Bezprozvanny
Summary: It has been found that RyanR is overactive in Alzheimer's disease (AD) and inhibiting RyanR may be beneficial for AD treatment. This study investigated the potential connection between basal RyanR activity and autophagy in neurons. The results showed that the basal RyanR2 activity inhibited autophagy through the calcineurin-AMPK-ULK1 pathway, and increased basal RyanR2 activity in AD may lead to the inhibition of neuronal autophagy and accumulation of β-amyloid. The findings suggest that reducing RyanR2 activity may be a potential target for therapeutic intervention in AD.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Cell Biology
Caiwang Peng, Fengyan Zhao, Hengli Li, Ling Li, Yantao Yang, Fang Liu
Summary: This article introduces the heat shock protein 90 (HSP90) as an important component of the molecular chaperone network, involved in cellular signaling pathways and stress response. It discusses the complex relationship between HSP90 and different types of programmed cell death (PCD) in various diseases, and proposes HSP90 as a potential common regulatory nodal for multiple PCD, offering a new perspective for disease therapies.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Tai-Mei Zhang, Li Liao, Shao-Ying Yang, Min-Ying Huang, Yin-Ling Zhang, Ling Deng, Shu-Yuan Hu, Fan Yang, Fang-Lin Zhang, Zhi-Min Shao, Da-Qiang Li
Summary: This study reveals the functional role of TMEM63A in triple-negative breast cancer (TNBC) and provides a new target for TNBC treatment. TMEM63A promotes TNBC cell proliferation, migration, and invasion, as well as tumor growth and lung metastasis in vivo. It interacts with VCP and DERL1 and is regulated by autophagic degradation mediated by TOLLIP. Inhibition of VCP or knockdown of DERL1 attenuates the oncogenic effects of TMEM63A in TNBC progression.
Article
Cardiac & Cardiovascular Systems
Yuxuan Guo, Yangpo Cao, Blake D. Jardin, Xiaoran Zhang, Pingzhu Zhou, Silvia Guatimosim, Junsen Lin, Zhan Chen, Yueyang Zhang, Neil Mazumdar, Fujian Lu, Qing Ma, Yao-Wei Lu, Mingming Zhao, Da-Zhi Wang, Erdan Dong, William T. Pu
Summary: The aim of this study is to investigate the role of RYR2 in cardiomyocyte maturation. The researchers used genetic editing techniques to knockout RYR2 and found that its depletion led to structural and transcriptional defects in cardiomyocytes, along with activation of ER stress pathways. The defects in RYR2-depleted cardiomyocytes were partially rescued by an ER stress alleviator.
CARDIOVASCULAR RESEARCH
(2023)
Review
Oncology
Hui Ming, Bowen Li, Jingwen Jiang, Siyuan Qin, Edouard C. Nice, Weifeng He, Tingyuan Lang, Canhua Huang
Summary: Despite progress in clinical management, drug resistance remains a major obstacle. Research on protein degradation has gained attention and several therapeutic strategies have been developed. Targeting the degradation process seems to be a more rapid and direct strategy compared to transcriptional intervention.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Teng Guan, Ting Zhou, Xiaosha Zhang, Ying Guo, Chaoxian Yang, Justin Lin, Jiasi Vicky Zhang, Yongquan Cheng, Hassan Marzban, Yu Tian Wang, Jiming Kong
Summary: Selective removal of misfolded SOD1 delays the onset of ALS, indicating that it is a promising treatment for the disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Damian Gatica, Mario Chiong, Sergio Lavandero, Daniel J. Klionsky
Summary: Macroautophagy/autophagy is a crucial cellular process involved in catabolic recycling, and dysregulation of autophagy is associated with cardiovascular diseases.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cell Biology
Camila Lopez-Crisosto, Alexis Diaz-Vegas, Pablo F. Castro, Beverly A. Rothermel, Roberto Bravo-Sagua, Sergio Lavandero
Summary: Subcellular organelles communicate and coordinate responses, with the physical coupling of the endoplasmic reticulum (ER) and mitochondria playing a key role in boosting mitochondrial metabolic activity. The mitochondrial unfolded protein response (mtUPR) is activated by unfolded proteins, leading to transcriptional responses aimed at restoring protein homeostasis. Increase in mitochondrial-ER coupling during mitochondrial stress can potentiate mitochondrial metabolic activity as a part of protective response.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Guangyu Zhang, Xiaoding Wang, Beverly A. Rothermel, Sergio Lavandero, Zhao Wang
Summary: Ischemic diseases, such as myocardial infarction and stroke, are among the deadliest and most disabling illnesses. The integrated stress response (ISR) plays a critical role in the pathogenesis and progression of ischemic diseases, making it a promising therapeutic target for alleviating symptoms and improving clinical outcomes of ischemic diseases such as ischemic heart disease, brain ischemia, ischemic liver disease, and ischemic kidney disease.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Cell Biology
David Mondaca-Ruff, Clara Quiroga, Ignacio Norambuena-Soto, Jaime A. Riquelme, Alejandra San Martin, Mario Bustamante, Sergio Lavandero, Mario Chiong
Summary: This study found that Ang II may regulate autophagy in VSMCs by transcriptional and translational mechanisms, increasing total LC3 content and LC3 processing. Additionally, Bag3 regulates Ang II-induced autophagy in VSMCs through the AT1R/ROCK signaling pathway.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Review
Genetics & Heredity
Leslye Venegas-Zamora, Francisco Bravo-Acuna, Francisco Sigcho, Wileidy Gomez, Jose Bustamante-Salazar, Zully Pedrozo, Valentina Parra
Summary: This article provides an overview of the genetic background of Down syndrome and the involvement of genes and non-coding RNAs in heart diseases. It also discusses the impact of altered pathways in cardiomyocytes and the role of mitochondrial and lysosomal dysfunction in heart function and development.
FRONTIERS IN GENETICS
(2022)
Letter
Cardiac & Cardiovascular Systems
Dan Tong, Gabriele G. Schiattarella, Nan Jiang, Daniel Daou, Yuxuan Luo, Mark S. Link, Sergio Lavandero, Thomas G. Gillette, Joseph A. Hill
Editorial Material
Cardiac & Cardiovascular Systems
Mario Chiong, Miles D. Houslay, Sergio Lavandero
Article
Biochemistry & Molecular Biology
Magda C. Diaz-Vesga, Raul Flores-Vergara, Jaime A. Riquelme, Marcelo Llancaqueo, Gina Sanchez, Cecilia Vergara, Luis Michea, Paulina Donoso, Andrew F. G. Quest, Ivonne Olmedo, Zully Pedrozo
Summary: Cardiomyopathy is commonly observed in patients with ADPKD, even without renal dysfunction or high blood pressure. This study investigated the role of PC1 in cardiovascular pathophysiology and found that decreased PC1 expression in cardiomyocytes induces dilated cardiomyopathy through reduced BIN1 expression and T-tubule remodeling. These findings suggest a novel pathway that may contribute to the development of cardiomyopathy in ADPKD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
Roberto Bravo-Sagua, Camila Lopez-Crisosto, Alfredo Criollo, Reiko Inagi, Sergio Lavandero
Summary: Organelles are membrane-lined structures that compartmentalize subcellular biochemical functions. Interorganelle communication is crucial for cellular responses. Evidence suggests that other organelles play important roles in pathophysiological conversation.
Article
Pharmacology & Pharmacy
Nicolas Herrera-Zelada, Ursula Zuniga-Cuevas, Andres Ramirez-Reyes, Ignacio Norambuena-Soto, Leslye Venegas-Zamora, Mayarling F. Troncoso, Alejandra Hernandez, Gina Sanchez, Zully Pedrozo, Sergio Lavandero, Jaime A. Riquelme
Summary: Small extracellular vesicles (SEVs), nanosized vesicles that transport biomolecules between cells, have potential applications as biomarkers, drug delivery tools, and therapeutic agents. SEVs of endothelial origin have been shown to reduce in vitro ischemia/reperfusion (I/R) injury, but the impact of endothelial inflammation on SEV functionality is unclear.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Hugo E. E. Verdejo, Adolfo Rojas, Camila Lopez-Crisosto, Fernando Baraona, Luigi Gabrielli, Vinicius Maracaja-Coutinho, Mario Chiong, Sergio Lavandero, Pablo F. F. Castro
Summary: This study investigated the role of trimetazidine in patients with PAH and found that it improved right ventricular function, remodeling, and functional class. Trimetazidine use was safe and well-tolerated, and it led to increased exercise capacity and minor improvements in RV remodeling.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Felipe Contreras-Briceno, Julian Vega, Jorge Mandiola, Maria Paz Ocaranza, Sebastian Herrera, Manuel Salinas, Rodrigo Fernandez, Jorge E. Jalil, Sergio Lavandero, Mario Chiong, Paz Godoy, Pablo F. Castro, Marta Sitges, Luigi Gabrielli
Summary: In male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2021)