The term mitochondrial disorders refers to a heterogeneous group of diseases affecting energetic metabolism and resulting in a variable impairment of mitochondrial respiratory chain. These disorders may strike single tissues and organs or show multisystem presentations.

Central Nervous System and skeletal muscle, due to their heavy reliance on oxidative metabolism, are often involved in mitochondrial disorders. As a consequence, mitochondrial disorders are often collectively termed “mitochondrial encephalomyopathies” and are mainly investigated by neurologists.

Mitochondrial disorders may be classified into two categories, on genetic basis:

1) Disorders due to mutations within mitochondrial DNA (mtDNA)
2) Mitochondrial disorders caused by mutations in nuclear genes encoding fro mitochondrial proteins.

The Laboratory of Biochemistry and Genetics has developed equipment and a strong know-how to face the challenge of the diagnosis of the mitochondrial disorders. We are particularly involved in study of disorders resulting from an impaired maintenance of mitochondrial DNA or originating from matrilineal mutations inherited along the mitochondrial DNA.

Southern blot analysis of mitochondrial DNA is the classical technique used to detect macro-rearrangements such as single deletion, multiple deletions and duplications.

In adult patients, this method is able to disclose the presence of mitochondrial genomes featuring a partial or improper replication or repair, resulting in the accumulation of multiple mitochondrial DNA deletions in post mitotic tissues, including skeletal muscle. This analysis is complemente by novel approaches based on conventional or quantitative PCR.

The presence of specific single nucleotide mutations within mitochondrial DNA is conveniently performed by Restriction Fragment Length Polymorphism analysis. We also perform the whole sequencing of mitochondrial DNA using an automated platform for DNA analysis based on capillary electrophoresis. Biochemical studies in patients’ tissues and cells are also fundamental to evaluate the impact of nuclear and mitochondrial DNA mutations on the activity of mitochondrial respiratory chain.

Primary culture cells obtained from skin and muscle biopsy constitute useful and reliable models to address biochemical and genetic features of mitochondrial disorders in vitro, contributing to confirm the diagnosis and formulate a prognosis.