Complement C1q Binding Protein (C1QBP): Physiological Functions, Mutation-Associated Mitochondrial Cardiomyopathy and Current Disease Models

Abstract

Complement C1q binding protein (C1QBP, p32) is primarily localized in mitochondrial matrix and associated with mitochondrial oxidative phosphorylative function. C1QBP deficiency presents as a mitochondrial disorder involving multiple organ systems. Recently, disease associated C1QBP mutations have been identified in patients with a combined oxidative phosphorylation deficiency taking an autosomal recessive inherited pattern. The clinical spectrum ranges from intrauterine growth restriction to childhood (cardio) myopathy and late-onset progressive external ophthalmoplegia. This review summarizes the physiological functions of C1QBP, its mutation-associated mitochondrial cardiomyopathy shown in the reported available patients and current experimental disease platforms modeling these conditions.

Keywords: C1QPB; combined oxidative phosphorylation deficiency; disease models; mitochondrial cardiomyopathies; mutation; physiological functions.

Figure 1

C1QBP variants in gene and protein structure. (A) Gene structure with exons and introns showing the localization of the variants. (B) Secondary structure of the C1QBP indicating the positions of the variants. MTS indicates the mitochondrial target sequence. (C) Inspection of the C1QBP structure performed using PyMOL (PDB accession codes 1P32, https://www.rcsb.org/structure/1P32). a: Predicted three-dimensional structure of the C1QBP protein; b and d: wild type; c, e and f: mutation type. Residue changes are colored in the structure: Cys186, yellow; Ser186, lemon; Tyr188, magenta; Phe204, cyan; Leu204, green-cyan; Gly247, blue; Trp247, purple-blue; Val248, green; Ala248, forest; Leu275, red; Phe275, brown; Pro275, warm pink.