Mitochondria are dynamic organelles which undergo fusion and fission processes responsible for mitochondrial network rearrangements. When mitochondria are damaged, they are selectively degraded via mitophagy. Collectively, these processes are referred to as “mitochondrial dynamics”, and are dysregulated in Parkinson’s disease (PD). Mutations in mitophagy-related PRKN gene, which encodes the E3 ubiquitin ligase Parkin, have been linked to autosomal recessive juvenile PD. Recently, Rab proteins, molecular players of the endo-lysosomal pathway, have been linked to mitophagy, and mutations in RAB32 and RAB39B have been identified to cause familial PD. To elucidate the interplay between Rab proteins and dysfunctional mitophagy in PD, we exploited PRKN-mutated human skin fibroblasts (vs. controls) to evaluate levels and sub-cellular localization of a Rab proteins’ subset. First, to increase fibroblasts susceptibility to mitochondrial damage, we induced a metabolic reprogramming toward oxidative phosphorylation by switching from a high-glucose culture medium to a galactose medium. As a result, we observed an increase of mitochondrial marker proteins levels coupled to the up-regulation of Rab7 protein levels, hinting a possible role in mitochondrial biogenesis. Then, to induce mitophagy we exploited two mitochondrial toxins related to PD, i.e., Rotenone and 1-methyl-4-phenylpyridinium (MPP+), either alone or in combination with metabolic reprogramming. We observed a reduction of the mitochondrial mass paralleled by an increase of the levels of Rab proteins, particularly Rab5. Collectively, our results support a possible role of Rab proteins in dysfunctional mitochondrial dynamics related to PD which deserves further investigations in terms of Rab proteins functionality and localization.