The impairment of HCCS leads to MLS syndrome by activating a non-canonical cell death pathway in the brain and eyes.

ABSTRACT: Mitochondrial-dependent (intrinsic) programmed cell death (PCD) is an essential homoeostatic mechanism that selects bioenergetically proficient cells suitable for tissue/organ development. However, the link between mitochondrial dysfunction, intrinsic apoptosis and developmental anomalies has not been demonstrated to date. Now we provide the evidence that non-canonical mitochondrial dependent apoptosis explains the phenotype of microphthalmia with linear skin lesions (MLS), an X-linked developmental disorder caused by mutations in the holocytochrome c-type synthase (HCCS)gene [corrected]. By taking advantage of a medaka model that recapitulates the MLS phenotype we demonstrate that downregulation of hccs, an essential player of the mitochondrial respiratory chain (MRC), causes increased ce

SUBMITTER: Indrieri A 

PROVIDER: S-EPMC3569643 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature