bims-miptne 2024-07-07 papers

Circ Res. 2024 Jul 05. 135(2): 372-396

Mitochondrial Structure and Function in Human Heart Failure.

Antentor Hinton, Steven M Claypool, Kit Neikirk, Nanami Senoo, Celestine N Wanjalla, Annet Kirabo, Clintoria R Williams.

Despite clinical and scientific advancements, heart failure is the major cause of morbidity and mortality worldwide. Both mitochondrial dysfunction and inflammation contribute to the development and progression of heart failure. Although inflammation is crucial to reparative healing following acute cardiomyocyte injury, chronic inflammation damages the heart, impairs function, and decreases cardiac output. Mitochondria, which comprise one third of cardiomyocyte volume, may prove a potential therapeutic target for heart failure. Known primarily for energy production, mitochondria are also involved in other processes including calcium homeostasis and the regulation of cellular apoptosis. Mitochondrial function is closely related to morphology, which alters through mitochondrial dynamics, thus ensuring that the energy needs of the cell are met. However, in heart failure, changes in substrate use lead to mitochondrial dysfunction and impaired myocyte function. This review discusses mitochondrial and cristae dynamics, including the role of the mitochondria contact site and cristae organizing system complex in mitochondrial ultrastructure changes. Additionally, this review covers the role of mitochondria-endoplasmic reticulum contact sites, mitochondrial communication via nanotunnels, and altered metabolite production during heart failure. We highlight these often-neglected factors and promising clinical mitochondrial targets for heart failure.

Keywords: cardiovascular diseases; heart failure; hypertension; mitochondria; myocardium

DOI: https://doi.org/10.1161/CIRCRESAHA.124.323800

Cell Signal. 2024 Jul 02. pii: S0898-6568(24)00252-3. [Epub ahead of print] 111284

Mitochondrial calcium uniporter complex: Unveiling the interplay between its regulators and calcium homeostasis.

Jin Guo, Yukun Wang, Chunxia Shi, Danmei Zhang, Qingqi Zhang, Luwen Wang, Zuojiong Gong.

The mitochondrial calcium uniporter complex (MCUc), serving as the specific channel for calcium influx into the mitochondrial matrix, is integral to calcium homeostasis and cellular integrity. Given its importance, ongoing research spans various disease models to understand the properties of the MCUc in pathophysiological contexts, but reported a different conclusion. Therefore, this review delves into the profound connection between MCUc-mediated calcium transients and cellular signaling pathways, mitochondrial dynamics, metabolism, and cell death. Additionally, we shed light on the recent advancements concerning the structural intricacies and auxiliary components of the MCUc in both resting and activated states. Furthermore, emphasis is placed on novel extrinsic and intrinsic regulators of the MCUc and their therapeutic implications across a spectrum of diseases. Meanwhile, we employed molecular docking simulations and identified candidate traditional Chinese medicine components with potential binding sites to the MCUc, potentially offering insights for further research on MCUc modulation.

Keywords: Calcium homeostasis; Mitochondrial calcium uniporter complex; Mitochondrial pathophysiology

DOI: https://doi.org/10.1016/j.cellsig.2024.111284

Front Mol Biosci. 2024 ;11 1402910

Bioenergetic myths of energy transduction in eukaryotic cells.

Guy C Brown.

The study of energy transduction in eukaryotic cells has been divided between Bioenergetics and Physiology, reflecting and contributing to a variety of Bioenergetic myths considered here: 1) ATP production = energy production, 2) energy transduction is confined to mitochondria (plus glycolysis and chloroplasts), 3) mitochondria only produce heat when required, 4) glycolysis is inefficient compared to mitochondria, and 5) mitochondria are the main source of reactive oxygen species (ROS) in cells. These myths constitute a 'mitocentric' view of the cell that is wrong or unbalanced. In reality, mitochondria are the main site of energy dissipation and heat production in cells, and this is an essential function of mitochondria in mammals. Energy transduction and ROS production occur throughout the cell, particularly the cytosol and plasma membrane, and all cell membranes act as two-dimensional energy conduits. Glycolysis is efficient, and produces less heat per ATP than mitochondria, which might explain its increased use in muscle and cancer cells.

Keywords: Warburg effect; bioenergetics; cancer; cell metabolism; energetics; glycolysis; mitochondria; oxidative stress

DOI: https://doi.org/10.3389/fmolb.2024.1402910