Lysosome

• Article • 14 June 2021 Metabolomic profiling of single enlarged lysosomes • • • ORCID: orcid.org/0000-0003-0231-4401 • • • • • • • • • • • ORCID: orcid.org/0000-0002-8391-4013 • ORCID: orcid.org/0000-0002-3302-0927 • … • ORCID: orcid.org/0000-0002-1585-3749 Show authors Nature Methods volume 18, pages 788–798 ( 2021) Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. The accuracy and reliability of this technique were validated by supporting previous findings, such as the transportability of lysosomal cationic amino acids transporters such as PQLC2 and the lysosomal trapping of lysosomotropic, hydrophobic weak base drugs such as lidocaine. We derived metabolites from single lysosomes in various cell types and classified lysosomes into five major subpopulations based on their chemical and biological divergence. Senescence and carcinoma altered metabolic profiles of lysosomes in a type-specific manner. Thus, SLMS can open more avenues for investigating heterogeneous lysosomal metabolic changes during physiological ...

People with these disorders are missing important enzymes (proteins that speed up reactions in the body). Without those enzymes, the lysosome isn’t able to break down these substances. When that happens, they build up in cells and become toxic. They can damage cells and organs in the body. This article covers some of the most common lysosomal storage disorders. Types of Lysosomal Storage Disorders Each disorder affects a different enzyme and has its own set of symptoms. They include: Fabry disease : It affects your ability to make alpha-galactosidase A. This enzyme breaks down a fatty substance called globotriaosylceramide. Without the enzyme, this fat builds up in cells and damages them. Symptoms might include: • Pain, numbness, tingling, or burning in the hands and feet • Body aches • Fever • Tiredness • Red or purple • Trouble • Swelling in the lower legs, • Clouding of the • • • • • Abnormal Gaucher disease : A lack of glucocerebrosidase (GBA) causes this condition. This enzyme breaks down a fat called glucocerebroside. Without GBA, the fat builds up in the Gaucher disease comes in three types, each with different symptoms. In general, symptoms include: • • • Easy bleeding and bruising • Tiredness • Bone pain and • • • Krabbe disease: This affects the galactosylceramidase causes this condition. This enzyme helps make and maintain Symptoms start in the first few months of life and include: • Muscle • Stiff limbs • Trouble walking • • • Seizures Metachromatic leukodystro...

Lysosome Definition Lysosomes are specialized vesicles within cells that digest large molecules through the use of hydrolytic enzymes. Vesicles are small spheres of fluid surrounded by a lipid bilayer membrane, and they have roles in transporting molecules within the cell. Lysosomes are only found in animal cells; a human cell contains around 300 of them. Not only do they digest large molecules, they are also responsible for breaking down and getting rid of waste products of the cell. Lysosomes contain over 60 different enzymes that allow them to carry out these processes. Functions of the Lysosome Lysosomes digest many complex molecules such as carbohydrates, lipids, proteins, and nucleic acids, which the cell then recycles for other uses. The pH of lysosomes is acidic (around pH 5) because their hydrolytic enzymes function best at this pH instead of at the neutral pH of the rest of the cell. Hydrolytic enzymes specifically break down large molecules through hydrolysis. During the process of hydrolysis, a molecule of water is added to a substance, causing it to cleave. Like the digestive system of the human body, which breaks down food using enzymes, the lysosome can be thought of as the “digestive system” of the cell because it breaks down molecules using enzymes. Lysosomes digest several different kinds of molecules. They can digest food molecules that enter the cell into smaller pieces if an endocytic vesicle (a vesicle that brings particles into the cell) fuses with t...

Long known as terminal degradation stations, lysosomes have emerged as sophisticated signalling centres that govern cell growth, division and differentiation. Lysosomes interface physically and functionally with other organelles, and the master regulator mechanistic target of rapamycin complex 1 kinase is activated on lysosomes in response to nutrient and growth factor inputs. Lysosomes also enable autophagy, a ‘self-eating’ process essential for quality control and stress adaptation. Faulty execution of lysosomal growth and catabolic programmes drives cancer, neurodegeneration and age-related diseases. Open Access articles citing this article. • • Chih Hung Lo • & Jialiu Zeng Translational Neurodegeneration Open Access 08 June 2023 • • Kohei Tsujimoto • , Hyota Takamatsu • & Atsushi Kumanogoh Inflammation and Regeneration Open Access 12 May 2023 • • Xingyu Li • , Yongming Chen • … Junfeng Hao Cell Death Discovery Open Access 11 March 2023 Access options • Perera, R. M. & Zoncu, R. The lysosome as a regulatory hub. Annu. Rev. Cell Dev. Biol. 32, 223–253 (2016). • Settembre, C., Fraldi, A., Medina, D. L. & Ballabio, A. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat. Rev. Mol. Cell Biol. 14, 283–296 (2013). • Zhao, J., Benlekbir, S. & Rubinstein, J. L. Electron cryomicroscopy observation of rotational states in a eukaryotic V-ATPase. Nature 521, 241–245 (2015). • Jezegou, A. et al. Heptahelical protein PQLC2 is a lysosomal catio...

Exciting new discoveries have transformed the view of the lysosome from a static organelle dedicated to the disposal and recycling of cellular waste to a highly dynamic structure that mediates the adaptation of cell metabolism to environmental cues. Lysosome-mediated signalling pathways and transcription programmes are able to sense the status of cellular metabolism and control the switch between anabolism and catabolism by regulating lysosomal biogenesis and autophagy. The lysosome also extensively communicates with other cellular structures by exchanging content and information and by establishing membrane contact sites. It is now clear that lysosome positioning is a dynamically regulated process and a crucial determinant of lysosomal function. Finally, growing evidence indicates that the role of lysosomal dysfunction in human diseases goes beyond rare inherited diseases, such as lysosomal storage disorders, to include common neurodegenerative and metabolic diseases, as well as cancer. Together, these discoveries highlight the lysosome as a regulatory hub for cellular and organismal homeostasis, and an attractive therapeutic target for a broad variety of disease conditions. Open Access articles citing this article. • • James L. Daly • , Chris M. Danson • … Peter J. Cullen Nature Communications Open Access 29 May 2023 • • Kohei Tsujimoto • , Hyota Takamatsu • & Atsushi Kumanogoh Inflammation and Regeneration Open Access 12 May 2023 • • Ting Wang • , Yi Qin • … Zheng Li Ac...