ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid Treatment.

ABSTRACT:

Background

Mutations in ADCK4 (aarF domain containing kinase 4) generally manifest as steroid-resistant nephrotic syndrome and induce coenzyme Q₁₀ (CoQ₁₀) deficiency. However, the molecular mechanisms underlying steroid-resistant nephrotic syndrome resulting from ADCK4 mutations are not well understood, largely because the function of ADCK4 remains unknown.

Methods

To elucidate the ADCK4's function in podocytes, we generated a podocyte-specific, Adck4-knockout mouse model and a human podocyte cell line featuring knockout of ADCK4. These knockout mice and podocytes were then treated with 2,4-dihydroxybenzoic acid (2,4-diHB), a CoQ₁₀ precursor analogue, or with a vehicle only. We also performed proteomic mass spectro

SUBMITTER: Widmeier E 

PROVIDER: S-EPMC7269352 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature