bims-mionch 2024-09-01 papers

Issue of 2024–09–01
four papers selected by
Gun Kim, Seoul National University

Curr Top Membr. 2024 ;pii: S1063-5823(24)00020-6. [Epub ahead of print]93 85-116

Lysosomal membrane contact sites: Integrative hubs for cellular communication and homeostasis.

Sumit Bandyopadhyay, Daniel Adebayo, Eseiwi Obaseki, Hanaa Hariri.

Lysosomes are more than just cellular recycling bins; they play a crucial role in regulating key cellular functions. Proper lysosomal function is essential for growth pathway regulation, cell proliferation, and metabolic homeostasis. Impaired lysosomal function is associated with lipid storage disorders and neurodegenerative diseases. Lysosomes form extensive and dynamic close contacts with the membranes of other organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and lipid droplets. These membrane contacts sites (MCSs) are vital for many lysosomal functions. In this chapter, we will explore lysosomal MCSs focusing on the machinery that mediates these contacts, how they are regulated, and their functional implications on physiology and pathology.

Keywords: Lipid homeostasis; Lysosomes; Membrane contact sites; Nutrient sensing; Organelles communication

DOI: https://doi.org/10.1016/bs.ctm.2024.07.001

Biogerontology. 2024 Aug 28.

Mitochondria: fundamental characteristics, challenges, and impact on aging.

Runyu Liang, Luwen Zhu, Yongyin Huang, Jia Chen, Qiang Tang.

As one of the most vital organelles within biological cells, mitochondria hold an irreplaceable status and play crucial roles in various diseases. Research and therapies targeting mitochondria have achieved significant progress in numerous conditions. Throughout an organism's lifespan, mitochondrial dynamics persist continuously, and due to their inherent characteristics and various external factors, mitochondria are highly susceptible to damage. This susceptibility is particularly evident during aging, where the decline in biological function is closely intertwined with mitochondrial dysfunction. Despite being an ancient and enigmatic organelle, much remains unknown about mitochondria. Here, we will explore the past and present knowledge of mitochondria, providing a comprehensive review of their intrinsic properties and interactions with nuclear DNA, as well as the challenges and impacts they face during the aging process.

Keywords: Aging; Endosymbiosis; Mitochondria; Mitochondria DNA; Nuclear DNA

DOI: https://doi.org/10.1007/s10522-024-10132-8

Cell Metab. 2024 Aug 13. pii: S1550-4131(24)00326-7. [Epub ahead of print]

Mitochondrial membrane lipids in the regulation of bioenergetic flux.

Stephen Thomas Decker, Katsuhiko Funai.

Oxidative phosphorylation (OXPHOS) occurs through and across the inner mitochondrial membrane (IMM). Mitochondrial membranes contain a distinct lipid composition, aided by lipid biosynthetic machinery localized in the IMM and class-specific lipid transporters that limit lipid traffic in and out of mitochondria. This unique lipid composition appears to be essential for functions of mitochondria, particularly OXPHOS, by its effects on direct lipid-to-protein interactions, membrane properties, and cristae ultrastructure. This review highlights the biological significance of mitochondrial lipids, with a particular spotlight on the role of lipids in mitochondrial bioenergetics. We describe pathways for the biosynthesis of mitochondrial lipids and provide evidence for their roles in physiology, their implications in human disease, and the mechanisms by which they regulate mitochondrial bioenergetics.

Keywords: bioenergetics; mitochondria; phospholipids

DOI: https://doi.org/10.1016/j.cmet.2024.07.024

Pharmacol Ther. 2024 Aug 22. pii: S0163-7258(24)00130-X. [Epub ahead of print]262 108710

Targeting organ-specific mitochondrial dysfunction to improve biological aging.

Corina T Madreiter-Sokolowski, Ursula Hiden, Jelena Krstic, Katrin Panzitt, Martin Wagner, Christian Enzinger, Michael Khalil, Mahmoud Abdellatif, Ernst Malle, Tobias Madl, Elena Osto, Markus Schosserer, Christoph J Binder, Andrea Olschewski.

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function. The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics. We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues. In conclusion, this review highlights the therapeutic potential of addressing mitochondrial dysfunction to mitigate organ-specific aging, focusing on the skin, liver, lung, brain, skeletal muscle, and lung, as well as on the reproductive, immune, and cardiovascular systems. Based on a comprehensive understanding of the multifaceted roles of mitochondria, innovative therapeutic strategies may be developed and optimized to combat biological aging and promote healthy aging across diverse organ systems.

Keywords: Anti-aging strategies; Mitochondrial dysfunction; Organ-specific aging; ROS homeostasis; Therapeutic interventions

DOI: https://doi.org/10.1016/j.pharmthera.2024.108710