Current approaches to reduce or eliminate mitochondrial DNA mutations

Mitochondrial DNA(mt DNA)mutations have been implicated in a broad range of disorders which severely affect human health(Wallace,1999).Some drugs have been developed to slow down pathological changes of mitochondrial disorders.However,there is no effective treatment for patients with mt DNA mutations.mt DNA is less protected and has fewer repair mechanisms than nuclear DNA(n DNA).Such a reality results in a much higher

Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space

Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction pathways.The intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanating from the respiratory chain.The optic atrophy 1(OPA1),an important protein for mitochondrial fusion,is cleaved into soluble short-form(S-OPA1)under stresses.Here we report that S-OPA1 could function as a molecular chaperone in IMS.We purified the S-OPA1(amino acid sequence after OPA1 isoform 5 S1 site)protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli(E.coli).We also showed that S-OPA1 conferred thermotolerance on IMS proteins,e.g.,neurolysin.The chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.