Ups and Downs of Lysosomal PH: Conflicting Roles of LAMP Proteins?

Overview

Journal Autophagy

Specialty Cell Biology

Date 2023 Nov 14

PMID 37960894

Authors

Jonathan Handy

Gustavo C MacIntosh

Andreas Jenny

Affiliations

Soon will be listed here.

Abstract

The acidic pH of lysosomes is critical for catabolism in eukaryotic cells and is altered in neurodegenerative disease including Alzheimer and Parkinson. Recent reports using Drosophila and mammalian cell culture systems have identified novel and, at first sight, conflicting roles for the lysosomal associated membrane proteins (LAMPs) in the regulation of the endolysosomal system. AD: Alzheimer disease; LAMP: lysosomal associated membrane protein; LTR: LysoTracker; PD: Parkinson disease; TMEM175: transmembrane protein 175; V-ATPase: vacuolar-type H-translocating ATPase.

References

Yim W, Mizushima N . Lysosome biology in autophagy. Cell Discov. 2020; 6:6. PMC: 7010707. DOI: 10.1038/s41421-020-0141-7. View

Eskelinen E . Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med. 2006; 27(5-6):495-502. DOI: 10.1016/j.mam.2006.08.005. View

Hu M, Li P, Wang C, Feng X, Geng Q, Chen W . Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes. Cell. 2022; 185(13):2292-2308.e20. PMC: 9236176. DOI: 10.1016/j.cell.2022.05.021. View

Kuo S, Tasset I, Cheng M, Diaz A, Pan M, Lieberman O . Mutant glucocerebrosidase impairs α-synuclein degradation by blockade of chaperone-mediated autophagy. Sci Adv. 2022; 8(6):eabm6393. PMC: 11809618. DOI: 10.1126/sciadv.abm6393. View

Pradas E, Martinez-Vicente M . The Consequences of GBA Deficiency in the Autophagy-Lysosome System in Parkinson's Disease Associated with GBA. Cells. 2023; 12(1). PMC: 9818455. DOI: 10.3390/cells12010191. View

Chaudhry N, Sica M, Surabhi S, Hernandez D, Mesquita A, Selimovic A . Lamp1 mediates lipid transport, but is dispensable for autophagy in . Autophagy. 2022; 18(10):2443-2458. PMC: 9542896. DOI: 10.1080/15548627.2022.2038999. View

Kinghorn K, Gronke S, Castillo-Quan J, Woodling N, Li L, Sirka E . A Drosophila Model of Neuronopathic Gaucher Disease Demonstrates Lysosomal-Autophagic Defects and Altered mTOR Signalling and Is Functionally Rescued by Rapamycin. J Neurosci. 2016; 36(46):11654-11670. PMC: 5125225. DOI: 10.1523/JNEUROSCI.4527-15.2016. View

Zhang J, Zeng W, Han Y, Lee W, Liou J, Jiang Y . Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel. Mol Cell. 2023; 83(14):2524-2539.e7. PMC: 10528928. DOI: 10.1016/j.molcel.2023.06.004. View

Lee J, Yang D, Goulbourne C, Im E, Stavrides P, Pensalfini A . Faulty autolysosome acidification in Alzheimer's disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques. Nat Neurosci. 2022; 25(6):688-701. PMC: 9174056. DOI: 10.1038/s41593-022-01084-8. View

10.

Cabasso O, Paul S, Dorot O, Maor G, Krivoruk O, Pasmanik-Chor M . Mutated in its Ortholog Recapitulates Neuronopathic Gaucher Disease. J Clin Med. 2019; 8(9). PMC: 6780790. DOI: 10.3390/jcm8091420. View

11.

Garcia-Sanz P, Orgaz L, Bueno-Gil G, Espadas I, Rodriguez-Traver E, Kulisevsky J . N370S-GBA1 mutation causes lysosomal cholesterol accumulation in Parkinson's disease. Mov Disord. 2017; 32(10):1409-1422. DOI: 10.1002/mds.27119. View

12.

Rowland T, Sweet M, Mestroni L, Taylor M . Danon disease - dysregulation of autophagy in a multisystem disorder with cardiomyopathy. J Cell Sci. 2016; 129(11):2135-43. PMC: 4920246. DOI: 10.1242/jcs.184770. View

13.

Eskelinen E, Illert A, Tanaka Y, Schwarzmann G, Blanz J, von Figura K . Role of LAMP-2 in lysosome biogenesis and autophagy. Mol Biol Cell. 2002; 13(9):3355-68. PMC: 124165. DOI: 10.1091/mbc.e02-02-0114. View

14.

Schneede A, Schmidt C, Holtta-Vuori M, Heeren J, Willenborg M, Blanz J . Role for LAMP-2 in endosomal cholesterol transport. J Cell Mol Med. 2009; 15(2):280-95. PMC: 3822795. DOI: 10.1111/j.1582-4934.2009.00973.x. View

15.

Andrejewski N, Punnonen E, Guhde G, Tanaka Y, Lullmann-Rauch R, Hartmann D . Normal lysosomal morphology and function in LAMP-1-deficient mice. J Biol Chem. 1999; 274(18):12692-701. DOI: 10.1074/jbc.274.18.12692. View

16.

Rudnik S, Damme M . The lysosomal membrane-export of metabolites and beyond. FEBS J. 2020; 288(14):4168-4182. DOI: 10.1111/febs.15602. View

17.

Gegg M, Menozzi E, Schapira A . Glucocerebrosidase-associated Parkinson disease: Pathogenic mechanisms and potential drug treatments. Neurobiol Dis. 2022; 166:105663. DOI: 10.1016/j.nbd.2022.105663. View

18.

Wang L, Lin G, Zuo Z, Li Y, Byeon S, Pandey A . Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia. Sci Adv. 2022; 8(28):eabn3326. PMC: 9278864. DOI: 10.1126/sciadv.abn3326. View

19.

Rahmani Z, Surabhi S, Rojo-Cortes F, Dulac A, Jenny A, Birman S . Deficiency Enhances Sensitivity to α-Synuclein and Oxidative Stress in Models of Parkinson Disease. Int J Mol Sci. 2022; 23(21). PMC: 9657416. DOI: 10.3390/ijms232113078. View

20.

Bouhamdani N, Comeau D, Turcotte S . A Compendium of Information on the Lysosome. Front Cell Dev Biol. 2022; 9:798262. PMC: 8714965. DOI: 10.3389/fcell.2021.798262. View