Proto-oncogene FAM83A contributes to casein kinase 1-mediated mitochondrial maintenance and white adipocyte...

Area of Science:

• Cell Biology
• Metabolism
• Molecular Biology

Background:

• Family with sequence similarity 83 A (FAM83A) is recognized as a proto-oncogene involved in cancer progression.
• The physiological roles of FAM83A in non-cancerous processes, particularly in metabolic tissues, remain largely unexplored.

Purpose of the Study:

• To investigate the novel function of FAM83A in adipocyte differentiation and its underlying molecular mechanisms.
• To elucidate the role of FAM83A in maintaining mitochondrial function within adipose tissue.

Main Methods:

• Utilized an adipocyte-targeting fusion oligopeptide (FITC-ATS-9R) for in vivo knockdown of Fam83a in mouse white adipose tissue.
• Employed cultured 3T3-L1 adipocytes to assess the effects of Fam83a loss on lipogenesis and mitochondrial function.
• Investigated molecular interactions between FAM83A, casein kinase 1 (CK1), and mitochondrial protein complexes.

Main Results:

• Knockdown of Fam83a in mice led to reduced white adipose tissue mass, smaller adipocytes, and exacerbated mitochondrial damage, especially under a high-fat diet.
• Loss or knockdown of Fam83a in 3T3-L1 cells significantly repressed lipid droplet formation and downregulated key lipogenic genes.
• Inhibition of Fam83a impaired mitochondrial ATP production by blocking the electron transport chain, increased apoptosis, and disrupted the TOM40 complex formation.

Conclusions:

• FAM83A plays a critical role in adipocyte differentiation and the maintenance of mitochondrial integrity.
• FAM83A interacts with CK1 to regulate mitochondrial outer membrane permeability and facilitate CK1-driven lipogenesis.
• These findings establish FAM83A as a key regulator of mitochondrial function during adipogenesis, extending its known biological significance.