Mitochondria are cytoplasmic organelles in eukaryotic cells that accomplish several distinct vital functions, including oxidative phosphorylation (OXPHOS), metabolic pathways, and integration of signaling for apoptosis. Impaired OXPHOS, the common final pathway of mitochondrial metabolism, results in a variety of clinical manifestations, and the term mitochondrial disorders is currently ascribed to (mostly) genetic diseases of the respiratory chain associated with mitochondrial DNA mutation or nuclear DNA mutations. In addition, dysfunction of mitochondria could also result from three large groups of diseases with mitochondrial impairments: 1) secondary mitochondrial diseases which are provoked by mutations in the non-mitochondrial genome leading to mitochondriotoxic effects by mutated proteins or crucially altered regulatory processes, 2) acute mitochondrial insults due to ischemia, inflammation, and intoxications, and 3) changes of mitochondrial regulation and function in cancer cells. In any case, impaired mitochondrial function leads to cellular energetic depression which is characterized by diminished phosphorylation potentials, cytoplasmic and mitochondrial Ca2+ overload, and accumulation of ROS and toxic proteins. We present the clinical and laboratory features of a girl with combined respiratory chain defect and immunologic impairment that includes T-cell immunodeficiency and autoimmune reactions. In addition, a short overview on the current knowledge of immune system involvement in primary and secondary defects of the mitochondrial respiratory chain will be presented.

Temeljne medicinske znanosti,Kliničke medicinske znanosti