Mitochondrial nucleic acid binding proteins associated with diseases

Abstract

Mammalian mitochondrial DNA (mtDNA) exists in structures called nucleoids, which correspond to the configuration of nuclear DNA. Mitochondrial transcription factor A (TFAM), first cloned as an mtDNA transcription factor, is critical for packaging and maintaining mtDNA. To investigate functional aspects of TFAM, we identified many RNA-binding proteins as candidate TFAM interactors, including ERAL1 and p32. In this review, we first describe the functions of TFAM, replication proteins such as polymerase gamma and Twinkle, and mitochondrial RNA binding proteins. We describe the role of mitochondrial nucleic acid binding proteins within the mitochondrial matrix and two oxidative phosphorylation-related proteins within the mitochondrial intermembrane space. We then discuss how mitochondrial dysfunction is related to several diseases, including mitochondrial respiratory disease, Miller syndrome and cancer. We also describe p32 knockout mice, which are embryonic lethal and exhibit respiratory chain defects. Miller syndrome is a recessive disorder characterized by postaxial acrofacial dysostosis and caused by a mutation in. Finally, we explain that p32 and mitochondrial creatine kinase may be novel markers for the progression of prostate cancer.

Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA

“…As a first key finding, ClpP pathogenic variants trigger the protein accumulation of POLDIP2, LRPPRC, and GFM1 with high consistency between mammalian species and cell types. While POLDIP2 functions at the nucleoid and LRPPRC at the mitochondrial RNA granule modulating polyadenylation [ 41 , 42 , 65 , 66 ], GFM1 directly acts at mitoribosomes, and its excess was shown to impair translation [ 44 , 67 , 68 ]. Mitoribosomal dysfunction is considered a crucial site of pathology in Perrault syndrome, and these events occur upstream.…”

C9-ALS-Associated Proline-Arginine Dipeptide Repeat Protein Induces Activation of NLRP3 Inflammasome of HMC3 Microglia Cells by Binding of Complement Component 1 Q Subcomponent-Binding Protein (C1QBP), and Syringin Prevents This Effect

“…Many studies have shown that C1QBP is critical for mitochondrial biosynthesis, metabolism, and functional maintenance. C1QBP is involved in mitochondrial genome replication and regulates the activity of mitochondrial transcription factor A (TFAM), a key factor in packaging and maintaining mtDNA [55]. RECQ4 is a helicase involved in mt-DNA synthesis.…”

Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX With Its Interactors at the Nucleoid and RNA Granule

“…As a first key finding, ClpP pathogenic variants trigger the protein accumulation of POLDIP2, LRPPRC and GFM1 with high consistency between mammalian species and cell types. While POLDIP2 functions at the nucleoid and LRPPRC at the mitochondrial RNA granule modulating polyadenylation [40,41,63,64], GFM1 directly acts at mitoribosomes and its excess was shown to impair translation [43,65,66]. Mitoribosomal dysfunction is considered a crucial site of pathology in Perrault syndrome, and these events occur upstream.…”