bims-miptne 2024-08-25 papers

Front Mol Neurosci. 2024 ;17 1423132

Mechanism and treatment of intracerebral hemorrhage focus on mitochondrial permeability transition pore.

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, characterized by high mortality and a poor prognosis. Despite various treatment methods, there has been limited improvement in the prognosis of ICH over the past decades. Therefore, it is imperative to identify a feasible treatment strategy for ICH. Mitochondria are organelles present in most eukaryotic cells and serve as the primary sites for aerobic respiration and energy production. Under unfavorable cellular conditions, mitochondria can induce changes in permeability through the opening of the mitochondrial permeability transition pore (mPTP), ultimately leading to mitochondrial dysfunction and contributing to various diseases. Recent studies have demonstrated that mPTP plays a role in the pathological processes associated with several neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke and ischemia-reperfusion injury, among others. However, there is limited research on mPTP involvement specifically in ICH. Therefore, this study comprehensively examines the pathological processes associated with mPTP in terms of oxidative stress, apoptosis, necrosis, autophagy, ferroptosis, and other related mechanisms to elucidate the potential mechanism underlying mPTP involvement in ICH. This research aims to provide novel insights for the treatment of secondary injury after ICH.

Keywords: cerebral hemorrhage; mechanism; mitochondria; mitochondrial permeability transition pore; treatment

DOI: https://doi.org/10.3389/fnmol.2024.1423132

Mol Neurobiol. 2024 Aug 23.

The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders.

Yue Liu, Xiying Yu, Wei Jiang.

The mitochondrial pyruvate carrier (MPC) is a specific protein complex located in the inner mitochondrial membrane. Comprising a heterodimer of two homodimeric membrane proteins, mitochondrial pyruvate carrier 1 and mitochondrial pyruvate carrier 2, MPC connects cytoplasmic metabolism to mitochondrial metabolism by transferring pyruvate from the cytoplasm to the mitochondria. The nervous system requires substantial energy to maintain its function, and the mitochondrial energy supply is closely linked to neurological function. Mitochondrial dysfunction can induce or exacerbate intracerebral pathologies. MPC influences mitochondrial function due to its specific role as a pyruvate transporter. However, recent studies on MPC and mitochondrial dysfunction in neurological disorders have yielded controversial results, and the underlying mechanisms remain unclear. In this brief review, we provide an overview of the structure and function of MPC. We further discuss the potential mechanisms and feasibility of targeting MPC in treating Parkinson's disease, Alzheimer's disease, and cerebral ischemia/hypoxia injury. This review aims to offer insights into MPC as a target for clinical treatment.

Keywords: Metabolism; Mitochondrial dysfunction; Mitochondrial pyruvate carrier; Neurological disorders

DOI: https://doi.org/10.1007/s12035-024-04435-7

Cell Biol Toxicol. 2024 Aug 20. 40(1): 72

Metal ions overloading and cell death.

Yun Lai, Fen Fen Gao, Ruo Ting Ge, Rui Liu, Shumei Ma, Xiaodong Liu.

Cell death maintains cell morphology and homeostasis during development by removing damaged or obsolete cells. The concentration of metal ions whithin cells is regulated by various intracellular transporters and repositories to maintain dynamic balance. External or internal stimuli might increase the concentration of metal ions, which results in ions overloading. Abnormal accumulation of large amounts of metal ions can lead to disruption of various signaling in the cell, which in turn can produce toxic effects and lead to the occurrence of different types of cell deaths. In order to further study the occurrence and development of metal ions overloading induced cell death, this paper reviewed the regulation of Ca2+, Fe3+, Cu2+ and Zn2+ metal ions, and the internal mechanism of cell death induced by overloading. Furthermore, we found that different metal ions possess a synergistic and competitive relationship in the regulation of cell death. And the enhanced level of oxidative stress was present in all the processes of cell death due to metal ions overloading, which possibly due to the combination of factors. Therefore, this review offers a theoretical foundation for the investigation of the toxic effects of metal ions, and presents innovative insights for targeted regulation and therapeutic intervention. HIGHLIGHTS: • Metal ions overloading disrupts homeostasis, which in turn affects the regulation of cell death. • Metal ions overloading can cause cell death via reactive oxygen species (ROS). • Different metal ions have synergistic and competitive relationships for regulating cell death.

Keywords: Apoptosis; Autophagy; Cuprotosis; Ferroptosis; Ions overloading; Necrosis

DOI: https://doi.org/10.1007/s10565-024-09910-4