an-in-vitro-approach-to-study-mitochondrial-dysfunction-a-cybrid-model

An<em> In Vitro</em> Approach to Study Mitochondrial Dysfunction: A Cybrid Model

Deficiency of the mitochondrial respiratory chain complexes that carry out oxidative phosphorylation (OXPHOS) is the biochemical marker of human ...

Fondazione IRCCS Istituto Neurologico Carlo Besta

Pearson marrow pancreas syndrome (PMPS) is a sporadic mitochondrial disease, resulting from the clonal expansion of a mutated mitochondrial DNA (mtDNA) molecule bearing a macro-deletion, and therefore missing essential genetic information. PMPS is characterized by the presence of deleted (Δ) mtDNA that co-exist with the presence of a variable amount of wild-type mtDNA, a condition termed heteroplasmy. All tissues of the affected individual, including the haemopoietic system and the post-mitotic, highly specialized tissues (brain, skeletal muscle, and heart) contain the large-scale mtDNA deletion in variable amount. We generated human induced pluripotent stem cells (hiPSCs) from two PMPS patients, carrying different type of large-scale deletion.

Generation of two human iPSC lines, FINCBi002-A and FINCBi003-A, carrying heteroplasmic macrodeletion of mitochondrial DNA causing Pearson's syndrome.

More than 30 years after discovering Leber's hereditary optic neuropathy (LHON) as the first maternally inherited disease associated with homoplasmic mtDNA mutations, we still struggle to achieve effective therapies. LHON is characterized by selective degeneration of retinal ganglion cells (RGCs) and is the most frequent mitochondrial disease, which leads young people to blindness, in particular males. Despite that causative mutations are present in all tissues, only a specific cell type is affected. Our deep understanding of the pathogenic mechanisms in LHON is hampered by the lack of appropriate models since investigations have been traditionally performed in non-neuronal cells. Effective  models of LHON are now emerging, casting promise to speed our understanding of pathophysiology and test therapeutic strategies to accelerate translation into clinic. We here review the potentials of these new models and their impact on the future of LHON patients.

Andrea Cavaliere

Unit of Medical Genetics and Neurogenetics

Fondazione IRCCS Istituto Neurologico Carlo Besta

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

Andrea Cavaliere

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Unit of Medical Genetics and Neurogenetics

Fondazione IRCCS Istituto Neurologico Carlo Besta

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

Unit of Medical Genetics and Neurogenetics