Anoop Dhamera

Peroxisome biogenesis disorders (PBD) are a group of disorders caused by defects in the family of PEX genes. These defects lead to compromised function of peroxisomes, as seen in fatal diseases such as Zellweger Syndrome (ZS). Mechanisms for a possible ZS therapy include addressing the root of the disease—lack of peroxisomes. Intercellular organelle transfer is the process in which two cells exchange organelles through cellular signaling. Previous studies have shown mitochondria and lysosome-deficient cells receive the respective organelles from neighboring cells when in need. Due to these findings, peroxisome transfer can prove to be the start of novel therapies for ZS and PBD. The aim of this study was to explore conditions in which peroxisome transfer may be observed through an in vitro model. It was hypothesized that cellular stress may induce necessary signals to promote peroxisome transfer. Busulfan, cellular irradiation, lipopolysaccharides (LPS), and serum depletion were chosen as cellular stressors to analyze intercellular peroxisome transfer levels at varying concentrations. Cell viability and oxidative stress assays were used to measure toxicity and stress levels, respectively. Co-cultures, followed by flow cytometry, were used to quantify peroxisome transfer. All stressors, except busulfan, showed a statistically significant increase in peroxisome transfer, with the highest reaching 21-fold (p < 0.01), 7-fold (p < 0.01), and 13-fold (p < 0.05) increases, exhibited in the serum depletion, LPS, and cellular irradiation conditions, respectively. These findings suggest serum depletion, LPS, and cellular irradiation play a role in increasing the rate of peroxisome transfer in an in vitro model and expanding this system may provide the start for ZS therapy.