Article
Chemistry, Medicinal
William H. Parsons, Nicholas T. Rutland, Jennifer A. Crainic, Joaquin M. Cardozo, Alyssa S. Chow, Charlotte L. Andrews, Brendan K. Sheehan
Summary: Using activity-based protein profiling technology, we identified a series of sulfonyl esters and sulfonamides as inhibitors of the mitochondrial rhomboid protease PARL. These compounds showed high selectivity for PARL over the bacterial rhomboid protease GlpG. The reversible binding of these compounds to PARL in mammalian cells suggests their potential as PARL-selective inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Verena Siebert, Mara Silber, Elena Heuten, Claudia Muhle-Goll, Marius K. Lemberg
Summary: The intramembrane protease PARL plays a crucial role in mitochondrial protection by cleaving the mitophagy regulators PINK1 and PGAM5. The cleavage of PGAM5 is influenced by multiple hierarchical substrate features, including a membrane potential-dependent oligomeric switch.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Yongjian Guo, Chengju Luo, Yuening Sun, Wenjing Guo, Ruitian Zhang, Xin Zhang, Xue Ke, Libin Wei
Summary: Mitochondrial dynamics play an important role in the development and progression of cancer, and dysregulated dynamics are associated with metabolic adaptations. This study identified a dual inhibitor called oroxylin A (OA) that restricts glucose metabolism of hepatocellular carcinoma cells and inhibits mitochondrial fusion. Further results revealed that mitochondrial functional status and spare respiratory capacity (SRC) are closely correlated with mitochondrial metabolic plasticity in cancer cells and play important roles in susceptibility to glucose restriction therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Edita Polachova, Kathrin Bach, Elena Heuten, Stancho Stanchev, Anezka Ticha, Philipp Lampe, Pavel Majer, Thomas Langer, Marius K. Lemberg, Kvido Strisovsky
Summary: The study reveals that the inhibition of PARL can activate the PINK1/Parkin pathway, promoting mitophagy in the context of Parkinson's disease. This highlights the potential of ketoamide inhibitors for cell biological studies of rhomboid proteases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Nina Kunova, Henrieta Havalova, Gabriela Ondrovicova, Barbora Stojkovicova, Jacob A. Bauer, Vladena Bauerova-Hlinkova, Vladimir Pevala, Eva Kutejova
Summary: Mitochondrial proteins are transported into mitochondria using a sophisticated system, and their proper folding and assembly rely on the cleavage of targeting presequences. Mitochondrial processing peptidases play a crucial role in mitochondrial homeostasis and their malfunctions are linked to severe human diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xiangfeng Niu, Ethan Stancliffe, Susan J. Gelman, Lingjue Wang, Michaela Schwaiger-Haber, Joe L. Rowles, Leah P. Shriver, Gary J. Patti
Summary: In this study, an approach to resolve the fluxes of NADPH in the cytosol and mitochondria was introduced using deuterium tracing. It was found that challenges in the cytosol affected NADPH fluxes in the cytosol, while challenges in the mitochondria affected NADPH fluxes in the mitochondria. This work highlights the value of using proline labeling as a reporter system for studying compartmentalized metabolism and reveals independent regulation of NADPH homeostasis in the cytosol and mitochondria, without evidence for NADPH shuttle activity.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Engineering, Environmental
Gaolong Zhong, Yuanxu Li, Lei Li, Yihui Huo, Wenting Zhang, Tingyu Li, Feiyang Ma, Jianzhao Liao, Ying Li, Hui Zhang, Jianying Guo, Jiaqiang Pan, Wenlan Yu, Lianmei Hu, Zhaoxin Tang
Summary: This study revealed the impact of copper exposure on mitochondrial microRNA expression profiles in chicken livers, and identified mitomiR12294-5p and its target gene CISD1 as crucial regulators involved in copper-induced hepatotoxicity. The results showed that copper exposure induced mitochondrial oxidative damage and disrupted mitochondrial quality control in chicken livers and primary chicken embryo hepatocytes. Inhibition of mitomiR-12294-5p expression effectively alleviated copper-induced mitochondrial damage, while up-regulation of mitomiR-12294-5p expression exacerbated the damage. Additionally, overexpression of CISD1 rescued copper-induced mitochondrial damage, while knockdown of CISD1 reversed the mitigating effect of inhibiting mitomiR-12294-5p expression on copper-induced mitochondrial damage.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Review
Biochemistry & Molecular Biology
Karolina Szczepanowska, Aleksandra Trifunovic
Summary: Mitochondria rely on chaperones and proteases for protein homeostasis, with proteases like LON and ClpXP modulating essential functions beyond quality control. Impaired mitochondrial protease function is linked to various pathological conditions, and recent research has identified them as potential targets for anticancer therapies.
Review
Cell Biology
Annunziata Cascone, Maciej Lalowski, Dan Lindholm, Ove Eriksson
Summary: LACTB is a relatively unknown mitochondrial protein that may play important roles in lipid metabolism and tumorigenesis. Despite numerous studies, the precise biochemical and cell biological function of LACTB remains unclear. The recently published cryo-electron microscopy structure of LACTB's filamentous form provides valuable insights for further research. Resolving these questions will enhance our understanding of the physiological functions of LACTB in cells and organisms.
Review
Immunology
Shasha Chen, Zhiyong Liao, Pinglong Xu
Summary: Mitochondria play versatile roles in cellular processes and have emerged as critical components in innate immunity. This review provides a comprehensive exploration of the multifaceted mechanisms underlying the interactions between mitochondria and innate immune responses. It discusses the roles of healthy mitochondria as platforms for signalosome assembly, the release of mitochondrial components as signaling messengers, and the regulation of signaling via mitophagy. Additionally, it explores the impacts of mitochondrial proteins and metabolites on modulating innate immune responses, immune cell polarization, and their implications in infectious and inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yun Hee Kim, Taesoo Kim, Kon-Young Ji, In-Sik Shin, Joo Young Lee, Kwang Hoon Song, Bu-Yeo Kim
Summary: The impairment of the airway epithelium barrier function is a common histological feature in asthmatic patients. This study investigated the mechanism by which proteolytic allergens disrupt the epithelial barrier integrity. The findings suggest that Aspergillus oryzae protease induces mitochondrial reactive oxygen species (ROS), leading to mitochondrial dysfunction and subsequent impairment of cellular barrier integrity.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Joseph E. Friedlander, Ning Shen, Aozhuo Zeng, Sovannarith Korm, Hui Feng
Summary: This review discusses the critical role of mitochondrial protein quality control in monitoring and safeguarding mitochondrial health and integrity, as well as its association with tumorigenesis. Dysregulated mitochondrial protein quality control can lead to dysfunction and proteotoxicity, contributing to various human diseases including cancer. Recent advances targeting alterations in mitochondrial protein quality control components are being developed for anti-cancer drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Inna Rabinovich-Nikitin, Mina Rasouli, Cristine J. Reitz, Illana Posen, Victoria Margulets, Rimpy Dhingra, Tarak N. Khatua, James A. Thliveris, Tami A. Martino, Lorrie A. Kirshenbaum
Summary: This study reveals that the CLOCK gene transcriptionally coordinates mitochondrial quality control mechanisms in cardiac myocytes, regulating an adaptive stress response crucial for cell survival. Restoring CLOCK activity may be beneficial in reducing cardiac injury in individuals with disrupted circadian rhythms.
Review
Oncology
Ken Yamaguchi, Sachiko Kitamura, Yoko Furutake, Ryusuke Murakami, Koji Yamanoi, Mana Taki, Masayo Ukita, Junzo Hamanishi, Masaki Mandai
Summary: Ovarian clear cell carcinoma (CCC) is characterized by slow growth, glycogen accumulation, and resistance to conventional chemotherapies. High expression of HNF1B in CCC leads to metabolic alterations, including increased glutathione synthesis, activation of anaerobic glycolysis (the Warburg effect), and suppression of mitochondria. These metabolic changes enable CCC cells to adapt and survive in stressful environments.
Review
Cell Biology
Jiyao Song, Johannes M. Herrmann, Thomas Becker
Summary: Mitochondria contain a diverse array of proteins from two genomes and require synchronized gene expression for proper function. The mitochondrial proteome is highly adaptable and regulated by quality control systems to ensure cellular adaptation and functionality. Defects in mitochondrial protein quality control mechanisms can lead to proteotoxic insults and cell death, highlighting the critical importance of maintaining protein homeostasis in mitochondria.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)