MICOS13 – mitochondrial disease

Pathogenic variants in MICOS13 have been implicated in autosomal recessive mitochondrial disease based on limited patient observations. In a cohort of 30 patients from 24 unrelated families with suspected mitochondrial disorders, bi-genomic sequencing revealed nuclear gene defects including MICOS13 in at least one proband (PMID:37377599). Separately, a homozygous frameshift variant, c.13_29del (p.Trp6ProfsTer71)(PMID:32749073), was identified in a patient presenting with hepato-encephalopathy and mitochondrial DNA depletion syndrome, consistent with an autosomal recessive mode of inheritance.

Functional studies confirm loss-of-function as the disease mechanism: patient fibroblasts lacking MICOS13 show abolished protein levels and disrupted cristae junctions, while lentiviral complementation with wild-type MICOS13 restores respiratory chain activity (PMID:32749073). Furthermore, systematic deletion mapping identified essential GxxxG and WN motifs required for MIC13 stability and bridging MICOS subcomplexes, linking structural perturbation to disease phenotype (PMID:34271005). Key take-home: MICOS13 currently has limited clinical validity in mitochondrial disease but is supported by robust mechanistic data and emerging diagnostic utility.

References

• Frontiers in genetics • 2023 • Clinical and bi-genomic DNA findings of patients suspected to have mitochondrial diseases. PMID:37377599
• Molecular genetics & genomic medicine • 2020 • A novel homozygous variant in MICOS13/QIL1 causes hepato-encephalopathy with mitochondrial DNA depletion syndrome. PMID:32749073
• Biochimica et biophysica acta. Biomembranes • 2021 • Conserved GxxxG and WN motifs of MIC13 are essential for bridging two MICOS subcomplexes. PMID:34271005

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