Lysosomal multienzyme complex: pros and cons of working together

Area of Science:

• Cell Biology
• Biochemistry
• Genetics

Background:

• Lysosomes are crucial for cellular homeostasis, differentiation, and remodeling.
• Lysosomal hydrolases function in complexes for efficient substrate degradation.
• Protective protein/cathepsin A (PPCA), neuraminidase-1 (NEU1), and β-galactosidase (β-GAL) form a core lysosomal enzyme complex.

Purpose of the Study:

• To review novel functions of PPCA, NEU1, and β-GAL beyond their canonical degradative roles.
• To explore how studies of lysosomal storage disorders in mouse models have uncovered these new functions.
• To highlight the potential therapeutic implications of these findings.

Main Methods:

• Review of studies on mouse models of galactosialidosis, sialidosis, and GM1-gangliosidosis.
• Analysis of research on the biological roles of PPCA, NEU1, and β-GAL.
• Examination of lysosomal enzyme complex assembly and function.

Main Results:

• Mouse models revealed unexpected roles for PPCA, NEU1, and β-GAL beyond substrate degradation.
• These enzymes participate in cellular processes beyond their canonical lysosomal functions.
• Lysosomal enzyme complexes exhibit dynamic assembly and disassembly for substrate adaptation.

Conclusions:

• The functions of PPCA, NEU1, and β-GAL are more diverse than previously understood.
• Lysosomal storage disorder research has unveiled novel therapeutic targets.
• Understanding these enzymes' expanded roles may lead to new treatment strategies for lysosomal storage disorders.