bims-mikwok 2022-06-05 papers

Issue of 2022–06–05
three papers selected by
Avinash N. Mukkala, University of Toronto

J Cardiovasc Pharmacol. 2022 Feb 18.

Mitochondrial Transplantation: A Unique Treatment Strategy.

Manli Zhou, Yunfeng Yu, Ying Luo, Xiaoxin Luo, Yifan Zhang, Xiahui Zhou, Yilei Hu, Weixiong Jian.

Mitochondrial transplantation refers to the process of introducing isolated mitochondria into a damaged area of the heart or other organs. In the past decade, this technique has been continuously updated as the fundamental research on the repair of damaged cells or tissues. Particularly, in the field of heart protection from ischemia-reperfusion injury, the MT therapy has been developed to the clinical trial stage. Generally speaking, the goal of therapeutic intervention is to replace damaged mitochondria or increase the transfer of mitochondria between cells so as to improve mitochondrial dysfunction. In this review, we summarized the studies on mitochondrial transplantation conducted at different time nodes and outlined a range of different methods for delivering mitochondria into the target site. Finally, we described the applications of mitochondrial transplantation in different diseases, and discussed the clinical studies of human mitochondrial transplantation currently in progress as well as the problems that need to be overcome. We hope to provide new ideas for the treatment of mitochondrial defects related diseases.

DOI: https://doi.org/10.1097/FJC.0000000000001247

J Drug Target. 2022 Jun 02. 1-21

Targeted mitochondrial drugs for treatment of Myocardial ischemia-reperfusion injury.

Jin-Fu Peng, Oluwabukunmi Modupe Salami, Cai Lei, Dan Ni, Olive Habimana, Guang-Hui Yi.

Myocardial ischemia-reperfusion injury (MI/RI) refers to the further damage done to ischemic cardiomyocytes when restoring blood flow. A large body of evidence shows that MI/RI is closely associated with excessive production of mitochondrial reactive oxygen species, mitochondrial calcium overload, disordered mitochondrial energy metabolism, mitophagy, mitochondrial fission, and mitochondrial fusion. According to the way it affects mitochondria, it can be divided into mitochondrial quality abnormalities and mitochondrial quantity abnormalities. Abnormal mitochondrial quality refers to the dysfunction caused by the severe destruction of mitochondria, which then affects the balance of mitochondrial density and number, causing an abnormal mitochondrial quantity. In the past, most of the reports were limited to the study of the mechanism of myocardial ischemia-reperfusion injury, some of which involved mitochondria, but no specific countermeasures were proposed. In this review, we outline the mechanisms for treating myocardial ischemia-reperfusion injury from the direction of mitochondria and focus on targeted interventions and drugs to restore mitochondrial health during abnormal mitochondrial quality control and abnormal mitochondrial quantity control. This is an update in the field of myocardial ischemia-reperfusion injury.

Keywords: Myocardial ischemia-reperfusion injury; Targeted mitochondrial drugs; Targeting Mitochondrial quality control; Targeting Mitochondrial quantity control

DOI: https://doi.org/10.1080/1061186X.2022.2085728

IUBMB Life. 2022 May 30.

Mitochondrial E3 ubiquitin ligase 1 (MUL1) as a novel therapeutic target for diseases associated with mitochondrial dysfunction.

Ximena Calle, Valeria Garrido-Moreno, Erik Lopez, Ignacio Norambuena-Soto, Daniela Martínez, Allan Peñaloza-Otárola, Angelo Troncossi, Alejandra Guerrero-Moncayo, Angélica Ortega, Vinicius Maracaja-Coutinho, Valentina Parra, Mario Chiong, Sergio Lavandero.

Mitochondrial E3 ubiquitin ligase (MUL1) is a mitochondrial outer membrane-anchored protein-containing transmembrane domains in both its N- and C-terminal regions, where both are exposed to the cytosol. Interestingly the C-terminal region has a RING finger domain responsible for its E3 ligase activity, as ubiquitin or in SUMOylation, interacting with proteins related to mitochondrial fusion and fission, cell survival, and tumor suppressor proteins, such as Akt. Therefore, MUL1 is involved in various cellular processes, such as mitochondrial dynamics, inter-organelle communication, proliferation, mitophagy, immune response, inflammation and cell apoptosis. MUL1 is expressed at a higher basal level in the heart, immune system organs, and blood. Here, we discuss the role of MUL1 in mitochondrial dynamics and its function in various pathological models, both in vitro and in vivo. In this context, we describe the role of MUL1 in: (1) the inflammatory response, by regulating NF-κB activity, (2) cancer, by promoting cell death and regulating exonuclear function of proteins, such as p53 (3) neurological diseases, by maintaining communication with other organelles and interacting with proteins to eliminate damaged organelles and (4) cardiovascular diseases, by maintaining mitochondrial fusion/fission homeostasis. In this review, we summarize the latest advances in the physiological and pathological functions of MUL1. We also describe the different substrates of MUL1, acting as a positive or negative regulator in various pathologies associated with mitochondrial dysfunction. In conclusion, MUL1 could be a potential key target for the development of therapies that focus on ensuring the functionality of the mitochondrial network and, furthermore, the quality control of intracellular components by synchronously modulating the activity of different cellular mechanisms involved in the aforementioned pathologies. This, in turn, will guide the development of targeted therapies. This article is protected by copyright. All rights reserved.

Keywords: Akt; C1orf166; FLJ12875; GIDE; MAPL; MULAN; Mitochondrial E3 ubiquitin ligase 1; RNF218; cell death; inflammation; mitochondria morphology

DOI: https://doi.org/10.1002/iub.2657