Assessment of mitophagy in mt‐Keima <i>Drosophila</i> revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction <i>in vivo</i>

Abstract

Mitophagy has been implicated in mitochondrial quality control and in various human diseases. However, the study of <i>in vivo</i> mitophagy remains limited. We previously explored <i>in vivo</i> mitophagy using a transgenic mouse expressing the mitochondria-targeted fluorescent protein Keima (mt-Keima). Here, we generated mt-Keima <i>Drosophila</i> to extend our efforts to study mitophagy <i>in vivo</i>. A series of experiments confirmed that mitophagy can be faithfully and quantitatively measured in mt-Keima <i>Drosophila</i>. We also showed that alterations in mitophagy upon environmental and genetic perturbation can be measured in mt-Keima <i>Drosophila</i>. Analysis of different tissues revealed a variation in basal mitophagy levels in <i>Drosophila</i> tissues. In addition, we found a significant increase in mitophagy levels during <i>Drosophila</i> embryogenesis. Importantly, loss-of-function genetic analysis demonstrated that the phosphatase and tensin homolog-induced putative kinase 1 (PINK1)-Parkin pathway is essential for the induction of mitophagy <i>in vivo</i> in response to hypoxic exposure and rotenone treatment. These studies showed that the mt-Keima <i>Drosophila</i> system is a useful tool for understanding the role and molecular mechanism of mitophagy <i>in vivo</i>. In addition, we demonstrated the essential role of the PINK1-Parkin pathway in mitophagy induction in response to mitochondrial dysfunction.-Kim, Y. Y., Um, J.-H., Yoon, J.-H., Kim, H., Lee, D.-Y., Lee, Y. J., Jee, H. J., Kim, Y. M., Jang, J. S., Jang, Y.-G., Chung, J., Park, H. T., Finkel, T., Koh, H., Yun, J. Assessment of mitophagy in mt-Keima <i>Drosophila</i> revealed an essential role of the PINK1-Parkin pathway in mitophagy induction <i>in vivo</i>.