Involved Biomolecules Within Lysosomal Energy Sensing in Health and Disease

Dear Colleagues,

Two interconnected and antagonistic signaling pathways sense the energy status of cells at the lysosome. These pathways, the catabolic lysosomal 5’-AMP-activated kinase (L-AMPK) pathway and the anabolic mammalian target of rapamycin complex 1 (mTorc1) pathway, physically and functionally assemble around vacuolar H⁺-ATPases (V-ATPases) in lysosome membranes. When energy levels fluctuate, appropriate anabolic or catabolic signaling from them helps to restore cellular homeostasis. Tremendous amounts of data regarding the mechanisms involved in these fundamentally important pathways, as well as the many roles of the pathways in human health and disease, have emerged during the recent few years.  For example, recent data supports the idea that benefits derived from caloric restriction, including improved muscle strength, glucose metabolism, and longevity, are at least in part mediated through the lysosomal energy sensing system. Pathologies (including cancer; neurodegeneration; retinal diseases; periodontitis; post-menopausal and age-related osteoporosis; chronic kidney disease; chronic pain from arthritis and other causes; Sjogren’s syndrome; and various other diseases) have been linked to problems with lysosomal energy sensing. Efforts to pharmacologically regulate lysosomal energy sensing using agents, such as metformin and rapamycin, have shown promise as new treatments. Various pathways for regulating lysosomal energy sensing (including through deacetylation by sirtuin-based networks and by aldolase, as well as sensing fructose 1,6, bisphosphate) have recently come to light. It is likely that strategies for therapeutically regulating lysosomal energy sensing will lead to new means to treat many diseases and to improve health.

The goal of this Special Issue, entitled “Involved Biomolecules Within Lysosomal Energy Sensing in Health and Disease", is to provide a broad overview of the contribution of biomolecules linked to lysosomal energy sensing in health and in disease development and etiology. We welcome insights from the knowledge gained through the study of human subjects and animal models, and cellular-based research.

This Special Issue aims to provide awareness about how this rapidly developing field opens new and transformational approaches to both maintaining health and treating disease. Original research and well-balanced review articles in this area are welcome. Research areas of interest include, but are not limited to, underlying mechanisms of lysosomal energy sensing, lysosomal energy sensing in cancer, neurodegeneration, arthritis, autoinflammatory diseases, and aging. Articles can focus on single biomolecules (examples include aldolase, Sirtuin 1) or on how key complexes, vacuolar H⁺-ATPase, lysosomal AMPK, and mTorc1, interact to modulate catabolic and anabolic pathways and inflammation in various settings.

Dr. Xianrui Yang
Dr. L. Shannon Holliday
Guest Editors

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• lysosomal energy sensing
• vacuolar H+-ATPase (V-ATPase)
• 5’-AMP-activated kinase (AMPK)
• mammalian target of rapamycin (mTor)
• sirtuin
• aldolase
• TRPV1
• metformin
• rapamycin