Mouse midbrain dopaminergic neurons survive loss of the PD-associated mitochondrial protein CHCHD2.

ABSTRACT: Mutations in the mitochondrial protein CHCHD2 cause autosomal dominant Parkinson's disease characterized by the preferential loss of substantia nigra dopamine (DA) neurons. Therefore, understanding the function of CHCHD2 in neurons may provide vital insights into how mitochondrial dysfunction contributes to neurodegeneration in PD. To investigate the normal requirement and function of CHCHD2 in neurons, we first examined CHCHD2 levels and showed that DA neurons have higher CHCHD2 levels than other neuron types, both in vivo and in co-culture. We then generated mice with either a targeted deletion of CHCHD2 in DA neurons or a deletion in the brain or total body. All three models were viable, and loss of CHCHD2 in the brain did not cause degeneration of DA neurons. Mice lacking CHCHD2 in DA

SUBMITTER: Nguyen MK 

PROVIDER: S-EPMC9071413 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature