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Published on: August 10, 2021
Molecular and cellular basis of lysosomal transmembrane protein dysfunction
Raquel Ruivo1, Christine Anne, Corinne Sagné
1Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique UPR 1929, Université Paris Descartes, 13 rue Pierre et Marie Curie, 75005 Paris, France.
Biochimica Et Biophysica Acta
|January 17, 2009
Summary
Lysosomal storage diseases involve defects in membrane proteins crucial for lysosome function. This review explores molecular mechanisms of these diseases, including transport defects and impaired autophagy.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- Lysosomal membrane proteins are vital for lysosome function, including acidification, transport, and organelle fusion.
- Defects in these proteins lead to various lysosomal storage diseases and Danon disease.
Purpose of the Study:
- To review the molecular mechanisms of lysosomal storage diseases.
- To discuss diseases caused by defective transport across the lysosomal membrane.
- To explore the pathogenesis of Danon disease.
Main Methods:
- Literature review of molecular mechanisms.
- Analysis of genetic defects in lysosomal transport proteins.
- Examination of protein function in lysosomal pathways.
Main Results:
- Specific transporter defects identified in cystinosis, free sialic acid storage diseases, cobalamin F disease, and mucopolysaccharidosis type IIIC.
- Impaired proton/chloride exchange in osteopetrosis affects V-type ATPase function.
- TRPML1 cation channel mutations cause Mucolipidosis type IV; its precise function is debated.
- LAMP2 defects in Danon disease impact lysosome-autophagosome fusion and motility.
Conclusions:
- Lysosomal membrane protein defects underlie diverse storage disorders.
- Further research is needed to clarify mechanisms in osteopetrosis and Mucolipidosis type IV.
- LAMP2's role in autophagy and motility is key to understanding Danon disease.
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