Article
Biochemistry & Molecular Biology
Yue Wang, Heinrich Jasper, Sam Toan, David Muid, Xing Chang, Hao Zhou
Summary: Mitophagy and UPRmt, although slightly activated by myocardial stress, work together to maintain mitochondrial performance and protect against inflammation-related myocardial injury. Mitophagy modulation of UPRmt could be a potential therapeutic strategy for myocardial stress.
Article
Cell Biology
Haizhe Ji, Jin Wang, David Muid, Wei Song, Yinong Jiang, Hao Zhou
Summary: The mitochondrial unfolded protein response (UPRmt) is an adaptive transcriptional response that degrades abnormal or unfolded proteins through activation of proteases, chaperones, and antioxidant enzymes to restore mitochondrial function. It plays a cardioprotective role in myocardial ischemia/reperfusion (I/R) injuries by regulating oxidative stress, apoptosis-related proteins, and mitochondrial quality control mechanisms.
CELLULAR SIGNALLING
(2022)
Article
Environmental Sciences
Yi Zhao, Hui-Xin Li, Yu Luo, Jia-Gen Cui, Milton Talukder, Jin-Long Li
Summary: The study found that LYC can prevent DEHP-induced hepatic mitochondrial quality control disorder by alleviating histopathological alterations and mitochondrial biogenesis disorder, as well as suppressing the SIRT1-PGC-1 alpha axis, PINK1-mediated mitophagy, and UPRmt activation. The research highlights the potential implication of the SIRT1/PINK1/mitophagy axis and UPRmt in LYC's protective effects against DEHP-induced liver damage.
ENVIRONMENTAL POLLUTION
(2022)
Review
Biochemistry & Molecular Biology
Eva-Maria Eckl, Olga Ziegemann, Luisa Krumwiede, Evelyn Fessler, Lucas T. Jae
Summary: Mitochondrial fidelity is crucial for longevity and can be disrupted in various disease contexts. Tight homeostatic control and the activation of different mechanisms in response to stress are essential for maintaining mitochondrial function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Juan M. Suarez-Rivero, Carmen J. Pastor-Maldonado, Suleva Povea-Cabello, Monica Alvarez-Cordoba, Irene Villalon-Garcia, Marta Talaveron-Rey, Alejandra Suarez-Carrillo, Manuel Munuera-Cabeza, Diana Reche-Lopez, Paula Cilleros-Holgado, Rocio Pinero-Perez, Jose A. Sanchez-Alcazar
Summary: Mitochondrial dysfunction is a common feature in many diseases, and new therapeutic approaches such as activating UPRmt are being explored. UPRmt activation has shown potential benefits in neurodegenerative diseases, cardiopathies, and mitochondrial diseases, but overactivation could lead to undesired side effects.
Article
Cell Biology
Yu Ruan, Jiaqiao Hu, Yaping Che, Yanyan Liu, Zhenhuan Luo, Jin Cheng, Qi Han, He He, Qinghua Zhou
Summary: Mitochondrial dysfunction is a major factor in the development of neurological disorders. Mutations in CHCHD2 and CHCHD10, which encode proteins in the mitochondrial CHCH domain family, are associated with Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia. CHCHD2 and CHCHD10 interact with OMA1 to inhibit its activity, suppressing mitochondrial stress response and fusion. During mitochondria stress, CHCHD2 and CHCHD10 translocate to the cytosol and interact with eIF2a, reducing overactivation of the stress response. Knockdown of CHCHD2 and CHCHD10 leads to mitochondrial stress response, which is amplified by CCCP treatment.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Mikhaela B. Slavin, Jonathan M. Memme, Ashley N. Oliveira, Neushaw Moradi, David A. Hood
Summary: This article examines the adaptive plasticity of mitochondria within skeletal muscle and the regulation of this characteristic by signals under conditions of exercise and inactivity. It discusses the impact of exercise and disuse on mitochondrial quantity and quality, as well as the related regulatory networks.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Louise Uoselis, Runa Lindblom, Wai Kit Lam, Catharina J. Kung, Marvin Skulsuppaisarn, Grace Khuu, Thanh N. Nguyen, Danielle L. Rudler, Aleksandra Filipovska, Ralf B. Schittenhelm, Michael Lazarou
Summary: This study developed a functional proteomics framework called MitoPQ to investigate the role of UPRmt in maintaining proteostasis during stress. The UPRmt was found to play critical roles in protecting and repairing proteostasis, especially in oxidative phosphorylation metabolism. Additionally, the interaction between the UPRmt and PINK1/Parkin mitophagy promotes the recovery of oxidative phosphorylation when the UPRmt fails.
Review
Biochemistry & Molecular Biology
Eirini Lionaki, Ilias Gkikas, Nektarios Tavernarakis
Summary: Mitochondria play diverse and crucial roles in fundamental cellular processes and organismal function, and the protein import system is a key component linking mitochondrial and cellular homeostasis. Recent research indicates that the mitochondrial protein import system acts as a signaling hub, receiving inputs from other cellular compartments and adjusting its function accordingly. Impairment of protein import elicits adaptive responses both inside and outside mitochondria, and this review discusses the mechanisms of mitochondrial protein import regulation, with a focus on quality control, proteostatic and metabolic cellular responses triggered by its impairment.
Article
Cell Biology
Jonathan. M. M. Memme, Victoria. C. C. Sanfrancesco, David. A. A. Hood
Summary: Mitochondrial function is crucial for overall health and the mitochondrial unfolded protein response (UPRmt) plays a significant role in maintaining mitochondrial quality control. In this study, the transcription factor ATF4 was found to regulate mitochondrial homeostasis and myotube formation in muscle cells. ATF4 also facilitated enhanced mitochondrial networking, protein handling, and clearance of dysfunctional organelles, ultimately leading to the formation of a smaller pool of high-functioning mitochondria that are more responsive to contractile activity. These findings expand our understanding of ATF4 beyond its known functions and highlight its importance in regulating mitochondrial morphology, lysosomal biogenesis, and mitophagy in muscle cells.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Developmental Biology
Shaihla A. Khan, Laura Reed, William B. Schoolcraft, Ye Yuan, Rebecca L. Krisher
Summary: The quality of oocytes from women of advanced maternal age is affected by dysfunctional mitochondria. This study investigated the mechanisms controlling mitochondrial quality during maternal aging in mouse and human oocytes. The expression of proteins involved in the mitochondrial unfolded protein response (UPRmt) and mitophagy was found to be decreased in aged oocytes compared to young oocytes. Treatment with the mitochondrially targeted antioxidant mitoquinone (MQ) restored protein expression and improved developmental potential.
MOLECULAR HUMAN REPRODUCTION
(2023)
Review
Biochemistry & Molecular Biology
Ge Wang, Yumei Fan, Pengxiu Cao, Ke Tan
Summary: The mitochondrial unfolded protein response (UPRmt) is a protective transcriptional response that maintains mitochondrial proteostasis. It is regulated by similar and different factors in C. elegans and mammals. Cancer cells hijack UPRmt to promote mitochondrial repair and tumor growth. Targeting UPRmt to disrupt proteostasis in cancer cells represents a novel anticancer therapeutic strategy.
CELL AND BIOSCIENCE
(2022)
Review
Cell Biology
Hedong Lu, Xiaolei Wang, Min Li, Dongmei Ji, Dan Liang, Chunmei Liang, Yajing Liu, Zhiguo Zhang, Yunxia Cao, Weiwei Zou
Summary: The development and application of high-throughput omics technologies have led to a better understanding of mitochondrial biosynthesis metabolism and the pathogenesis of mitochondrial diseases, resulting in the emergence of new treatments. The mitochondrial unfolded protein response (UPRmt) is crucial for maintaining mitochondrial proteostasis and plays a fundamental role in the development of mitochondrial diseases. In mammals, the integrated stress response (ISR) and UPRmt are closely related and work together to maintain mitochondrial function, showing great potential in the treatment of mitochondrial diseases. This review provides an overview of the molecular mechanisms of ISR and UPRmt and highlights them as potential targets for mitochondrial disease therapy.
Article
Cell Biology
Jin Wang, Xiaohua Wang, Wenjuan Du, Zhe Xue, Wei Huang, Zhenpeng Guan, Hongyu Wang
Summary: This study suggests that upregulation of BI-1 expression may serve as a therapeutic approach for attenuating myocardial injury in CRS-3 by activating mitophagy and the UPRmt, thereby protecting cardiac function and reducing apoptosis and inflammation.
CELLULAR SIGNALLING
(2022)
Review
Cell Biology
Pascal Trouve, Claude Ferec, Emmanuelle Genin
Summary: The most common mutation in cystic fibrosis is p.Phe508del in the CFTR gene, leading to retention and rapid degradation of CFTR protein in the endoplasmic reticulum, triggering an atypical Unfolded Protein Response (UPR). There is still debate on the role of UPR in CF, whether it is triggered by accumulation of misfolded CFTR proteins or as a result of inflammation and infection in the disease.
