ASTROCYTE-DERIVED MITOCHONDRIA INTERCELLUAR TRANSFER, A POTENTIAL THREAT FOR STRIATAL NEURONS IN HUNTINGTON'S DISEASE

Mitochondrial dysfunction plays a central role in the pathogenesis of several neurodegenerative diseases. Particularly, in Huntington’s disease (HD) -an inherited neurodegenerative disorder characterized by psychiatric, cognitive and motor impairments -mitochondrial abnormalities are prominent. These mitochondrial dysfunctions, along with other cellular alterations, are most notably observed in neurons within the striatum, the brain region primarily affected in HD.
Under normal physiological conditions, astrocytes and neurons engage in a process known as transmitophagy, where mitochondria are exchanged between these cell types. This process is beneficial for neurons in terms of improving neuronal metabolism. However, the role of transmitophagy in neurodegenerative diseases remains largely unexplored. Our group is focused on describing the consequences of transmitophagy in striatum of R6/1 mouse model of HD. To address this aim, we described mitochondrial dysfunction in primary cultures of R6/1 striatal astrocytes and found increased oxidative stress and impaired branching after treating striatal cultured neurons with mitochondria-containing astrocyte conditioned mediums. Furthermore, we assessed the presence of astrocytic mitochondria within neurons in striatal tissue from R6/1 mice at different disease stages to evaluate mitochondrial transfer in vivo during disease progression.
In sum, our group has taken a further step in the study of intercellular mitochondrial transfer, suggesting a potential pathological role for this process in neurodegenerative diseases.