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Lysosomal biogenesis in lysosomal storage disorders
L E Karageorgos1, E L Isaac, D A Brooks
1Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, South Australia.
Experimental Cell Research
|July 10, 1997
Summary
Lysosomal biogenesis increases during storage vacuole formation in fibroblasts. Protein and mRNA levels rise, indicating a regulated process controlled at the mRNA level, even in storage disorders.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Lysosomal biogenesis involves synthesizing, targeting, and turning over lysosomal proteins.
- Storage vacuoles can form in normal and storage disorder-affected fibroblasts.
- Understanding lysosomal biogenesis is crucial for lysosomal storage diseases.
Purpose of the Study:
- To investigate lysosomal biogenesis during storage vacuole formation and dissipation.
- To analyze the regulation of lysosomal proteins and their mRNA during storage.
- To compare lysosomal biogenesis in normal and storage disorder fibroblasts.
Main Methods:
- Studied sucrosome formation in normal skin fibroblasts.
- Utilized storage disorder-affected skin fibroblasts.
- Quantified lysosomal proteins (e.g., LAMP-1) and mRNA levels (e.g., LAMP-1, LAMP-2).
Main Results:
- Lysosomal proteins and mRNAs were significantly elevated (2-28 fold) during lysosomal storage.
- Upregulation of protein and mRNA lagged 2-4 days behind storage vacuole formation.
- Correction of storage led to rapid mRNA decline and slower protein level decrease.
Conclusions:
- Lysosomal biogenesis in storage disorders is a regulated process.
- Regulation occurs at or prior to the mRNA level.
- Common mechanisms likely coordinate lysosomal biogenesis events.