Paraplegin is a human gene whose product c12orf65 (also known as mitochondrial release factor) is a mitochondrial matrix protein that functions as a peptide release factor in mitochondrial translation termination. It recognizes stop codons (UAA, UAG) in mitochondrial mRNA and catalyzes the release of newly synthesized polypeptides from the ribosome, a critical step in mitochondrial protein synthesis [1]. Variants in Paraplegin have been implicated in Combined Oxidative Phosphorylation Deficiency 7 (COXPD7), Leigh Syndrome Spectrum, Hereditary Spastic Paraplegia. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
C12orf65 (also known as mitochondrial release factor) is a mitochondrial matrix protein that functions as a peptide release factor in mitochondrial translation termination. It recognizes stop codons (UAA, UAG) in mitochondrial mRNA and catalyzes the release of newly synthesized polypeptides from the ribosome, a critical step in mitochondrial protein synthesis [1].
C12orf65 is essential for the production of mitochondrial-encoded subunits of the electron transport chain, particularly those of Complex IV (cytochrome c oxidase) and Complex V (ATP synthase). Loss of C12orf65 function leads to impaired oxidative phosphorylation and cellular energy deficiency, especially in high-energy-demand tissues like [neurons](/entities/neurons) [2].
Key functions include:
Stop codon recognition in mitochondrial translation
Biallelic C12orf65 mutations cause COXPD7, a severe mitochondrial disorder characterized by:
Progressive encephalopathy
Optic atrophy and vision loss
Spastic paraplegia
Axonal peripheral neuropathy
Leigh syndrome-like neuroimaging findings [3]
Leigh Syndrome Spectrum
C12orf65-related disorders frequently present with Leigh syndrome features, including bilateral symmetric brainstem and basal ganglia lesions on MRI, reflecting the vulnerability of these regions to mitochondrial dysfunction [4].
Hereditary Spastic Paraplegia
Some C12orf65 variants present primarily as a complicated hereditary spastic paraplegia with:
Progressive lower limb spasticity
Optic nerve involvement
Cognitive decline
Peripheral neuropathy
Expression
C12orf65 is ubiquitously expressed, with highest levels in: