Autophagy controls centrosome number by degrading Cep63

Area of Science:

• Cell Biology
• Genomics
• Molecular Biology

Background:

• Centrosome number is critical for chromosome segregation and maintaining genomic stability.
• The ubiquitin-proteasome system is a known regulator of centrosome number.
• The role of other cellular pathways, like autophagy, in centrosome regulation is less understood.

Purpose of the Study:

• To investigate the role of autophagy in regulating centrosome number.
• To identify the molecular mechanisms by which autophagy controls centrosome number.

Main Methods:

• Analysis of autophagy-deficient cells to assess centrosome number.
• Investigating the interaction between Cep63, p62, and autophagosomes.
• Utilizing mouse models (autophagy-deficient and p62-/-) to study centrosome regulation in vivo.

Main Results:

• Autophagy-deficient cells exhibit an increased number of centrosomes.
• The centrosomal protein Cep63 is degraded by autophagy.
• Cep63 is recruited to autophagosomes via p62, a key component of selective autophagy.
• Hematopoietic cells from autophagy-deficient and p62-/- mice also show increased centrosome numbers.

Conclusions:

• Autophagy acts as a crucial regulator of centrosome number.
• The degradation of Cep63 by autophagy is a key mechanism controlling centrosome homeostasis.
• Dysregulation of autophagy can lead to abnormal centrosome numbers and potentially affect genomic stability.