Defective autophagy in a fibroin secretion-deficient silkworm mutant

Area of Science:

• Cell Biology
• Genetics
• Biochemistry

Background:

• The silkworm (Bombyx mori) is vital for silk production, with silk glands synthesizing and secreting silk proteins.
• The naked pupa (Nd) mutant strain shows severe posterior silk gland (PSG) atrophy and abnormal silk protein secretion.

Purpose of the Study:

• Investigate the underlying mechanisms of PSG degeneration in Nd silkworms.
• Determine the role of autophagy and lysosomal function in Nd mutant silkworms.
• Explore potential therapeutic strategies for protein aggregation diseases using Nd silkworms as a model.

Main Methods:

• Analyzed autophagic marker (Atg8-PE) and substrate (SQSTM1/p62) levels in Nd silkworms.
• Assessed autophagic flux using bafilomycin A1 (BafA1) treatment.
• Evaluated lysosomal acidification and cathepsin L1 (CtsL1) maturation.
• Investigated the effect of acidic nanoparticles (aNP) on Nd-PSG.

Main Results:

• Up-regulation of Atg8-PE via the target of rapamycin complex 1 (TORC1) pathway was observed in Nd.
• Increased levels of SQSTM1/p62 and ubiquitinated proteins indicated impaired autophagic flux.
• Lysosomal acidification was abnormal, reducing mature CtsL1 and leading to protein aggregate accumulation.
• Acidic nanoparticles rescued lysosomal acidification and ameliorated PSG degenerative changes.

Conclusions:

• Impaired autophagic flux and lysosomal dysfunction cause protein aggregation and PSG degeneration in Nd silkworms.
• The Nd mutant silkworm serves as a valuable animal model for studying protein aggregation diseases.
• Acidic nanoparticles demonstrate therapeutic potential for protein aggregation-related disorders.