C57BL/6JCya-Micos13^em1flox/Cya

MICOS13, also known as QIL1, MIC13, or C19orf70, is a component of the MICOS complex. The MICOS complex is crucial for maintaining cristae junctions at the mitochondrial inner membrane, which are implicated in regulating oxidative phosphorylation, apoptosis, and import of lipids and proteins [1,4,5,6,7].

In a hepato-encephalopathy patient with mitochondrial DNA depletion syndrome (MTDPS), a novel homozygous frameshift variant, c.13_29del (p.Trp6Profs*71) in MICOS13 was identified. Loss of MICOS13 protein led to fewer cristae structures in the patient's fibroblasts, and stable expression of wild-type MICOS13 cDNA rescued mitochondrial respiratory chain complex deficiencies, suggesting this variant causes hepato-encephalopathy with MTDPS [1]. In other patients suspected of having mitochondrial diseases, exome sequencing revealed pathogenic variants in MICOS13 among other genes [2]. Additionally, a study on beef color stability found that in beef with intermediate ultimate pH packaged in vacuum, MICOS13 was upregulated, indicating enhanced mitochondrial integrity [3]. Conserved GxxxG and WN motifs of MIC13 are essential for bridging two MICOS subcomplexes, and deletion of these regions affects the stability and functionality of MIC13, leading to abnormal cristae morphology [4]. Knockout of MICOS13 in cells shows a complete loss of crista junctions, and it is required for the assembly of some MICOS subunits into the complex [5]. Mutations in MICOS13 are associated with early-onset fatal mitochondrial encephalopathy with liver disease, causing MICOS disassembly, abnormal cristae, and defects in respiratory chain function [6]. A novel mutation in the C19orf70 gene encoding QIL1 (MICOS13) induces severe mitochondrial encephalopathy, hepatopathy, and lactate acidosis, along with bilateral kidney stones, and leads to disassembly of the MICOS complex and aberrant cristae structure [7].

In conclusion, MICOS13 plays a fundamental role in maintaining mitochondrial ultrastructure, specifically in the formation of crista junctions and the assembly of the MICOS complex. Research on MICOS13, especially through functional studies in cell models and patients with mutations, has revealed its importance in mitochondrial-related diseases such as MTDPS, mitochondrial encephalopathy, and hepatopathy. These findings contribute to a better understanding of the pathogenesis of these diseases and may potentially guide future treatment strategies.