bims-mionch 2024-08-25 papers

Issue of 2024–08–25
four papers selected by
Gun Kim, Seoul National University

Rev Neurosci. 2024 Aug 20.

Unraveling mitochondrial dysfunction: comprehensive perspectives on its impact on neurodegenerative diseases.

Abdul Aziz Mohamed Yusoff, Siti Zulaikha Nashwa Mohd Khair.

Neurodegenerative diseases represent a significant challenge to modern medicine, with their complex etiology and progressive nature posing hurdles to effective treatment strategies. Among the various contributing factors, mitochondrial dysfunction has emerged as a pivotal player in the pathogenesis of several neurodegenerative disorders. This review paper provides a comprehensive overview of how mitochondrial impairment contributes to the development of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, driven by bioenergetic defects, biogenesis impairment, alterations in mitochondrial dynamics (such as fusion or fission), disruptions in calcium buffering, lipid metabolism dysregulation and mitophagy dysfunction. It also covers current therapeutic interventions targeting mitochondrial dysfunction in these diseases.

Keywords: mitochondrial bioenergetics and biogenesis; mitochondrial dynamics and mitophagy; mitochondrial dysfunctions; neurodegenerative diseases; therapy

DOI: https://doi.org/10.1515/revneuro-2024-0080

Biochem Soc Trans. 2024 Aug 22. pii: BST20240261. [Epub ahead of print]

Interplay of mitochondrial calcium signalling and reactive oxygen species production in the brain.

Plamena R Angelova, Andrey Y Abramov.

Intracellular communication and regulation in brain cells is controlled by the ubiquitous Ca2+ and by redox signalling. Both of these independent signalling systems regulate most of the processes in cells including the cell surviving mechanism or cell death. In physiology Ca2+ can regulate and trigger reactive oxygen species (ROS) production by various enzymes and in mitochondria but ROS could also transmit redox signal to calcium levels via modification of calcium channels or phospholipase activity. Changes in calcium or redox signalling could lead to severe pathology resulting in excitotoxicity or oxidative stress. Interaction of the calcium and ROS is essential to trigger opening of mitochondrial permeability transition pore - the initial step of apoptosis, Ca2+ and ROS-induced oxidative stress involved in necrosis and ferroptosis. Here we review the role of redox signalling and Ca2+ in cytosol and mitochondria in the physiology of brain cells - neurons and astrocytes and how this integration can lead to pathology, including ischaemia injury and neurodegeneration.

Keywords: calcium; glial cell; mitochondria; mitochondrial permeability transition pores; neuron; reactive oxygen species

DOI: https://doi.org/10.1042/BST20240261

Biochim Biophys Acta Bioenerg. 2024 Aug 20. pii: S0005-2728(24)00476-6. [Epub ahead of print]1865(4): 149506

Mitochondrial uncoupling caused by a wide variety of protonophores is differently sensitive to carboxyatractyloside in rat heart and liver mitochondria.

Ljudmila S Khailova, Roman S Kirsanov, Tatyana I Rokitskaya, Vladimir S Krasnov, Galina A Korshunova, Elena A Kotova, Yuri N Antonenko.

Mitochondrial uncoupling by small-molecule protonophores is generally accepted to proceed via transmembrane proton shuttling. The idea of facilitating this process by the adenine nucleotide translocase ANT originated primarily from the partial reversal of the DNP-induced mitochondrial uncoupling by the ANT inhibitor carboxyatractyloside (CATR). Recently, the sensitivity to CATR was also observed for the action of such potent OxPhos uncouplers as BAM15, SF6847, FCCP and niclosamide. Here, we report measurements of the CATR effect on the activity of a large number of conventional and novel uncouplers in isolated mammalian mitochondria. Despite the broad variety of chemical structures, CATR attenuated the uncoupling efficacy of all the anionic protonophores in rat heart mitochondria with high abundance of ANT, whereas the effect was much less pronounced or even absent, e.g. for SF6847, in rat liver mitochondria with low ANT content. The fact that the uncoupling action is tissue specific for a broad spectrum of anionic protonophores is highlighted here for the first time. Only with the cationic uncoupler ellipticine and the channel-forming peptide gramicidin A, no sensitivity to CATR was found even in rat heart mitochondria. By contrast, with the recently described ester-stabilized ylidic protonophores [Kirsanov et al. Bioelectrochemistry 2023], the stimulating effect of CATR was discovered both in liver and heart mitochondria.

Keywords: Adenine nucleotide translocator; Carboxyatractyloside; Membrane potential; Mitochondrial uncoupler; Protonophore; Respiration rate

DOI: https://doi.org/10.1016/j.bbabio.2024.149506