Abstract
The maintenance of mitochondrial homeostasis requires PTEN-induced kinase 1 (PINK1)-dependent mitophagy, and mutations in PINK1 are associated with Parkinson's disease (PD). PINK1 is also downregulated in tumor cells with PTEN mutations. However, there is limited information concerning the role of PINK1 in tissue growth and tumorigenesis. Here, we show that the loss of pink1 caused multiple growth defects independent of its pathological target, Parkin. Moreover, knocking down pink1 in muscle cells induced hyperglycemia and limited systemic organismal growth by the induction of Imaginal morphogenesis protein-Late 2 (ImpL2). Similarly, disrupting PTEN activity in multiple tissues impaired systemic growth by reducing pink1 expression, resembling wasting-like syndrome in cancer patients. Furthermore, the re-expression of PINK1 fully rescued defects in carbohydrate metabolism and systemic growth induced by the tissue-specific pten mutations. Our data suggest a function for PINK1 in regulating systemic growth in Drosophila and shed light on its role in wasting in the context of PTEN mutations.
Highlights
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and it is clear that mitochondrial dysfunction plays a key role in PD pathogenesis (Exner et al, 2012)
We demonstrate that pink1 deficiency results in multiple growth defects and that PTEN-induced kinase 1 (PINK1) in mitochondria controlled cell growth independent of Parkin
Downregulation of PINK1 interrupts insulin signaling through aberrant activation of Imaginal morphogenesis protein-Late 2 (ImpL2) We explored whether the growth-inhibitory effects associated with the loss of PINK1 were due to reduced systemic insulin signaling, a major endocrine regulator of carbohydrate homeostasis and body growth
Summary
The maintenance of mitochondrial homeostasis requires PTEN-induced kinase 1 (PINK1)-dependent mitophagy, and mutations in PINK1 are associated with Parkinson’s disease (PD). PINK1 is downregulated in tumor cells with PTEN mutations. There is limited information concerning the role of PINK1 in tissue growth and tumorigenesis. We show that the loss of pink caused multiple growth defects independent of its pathological target, Parkin. Knocking down pink in muscle cells induced hyperglycemia and limited systemic organismal growth by the induction of Imaginal morphogenesis protein-Late 2 (ImpL2). Disrupting PTEN activity in multiple tissues impaired systemic growth by reducing pink expression, resembling wasting-like syndrome in cancer patients. The re-expression of PINK1 fully rescued defects in carbohydrate metabolism and systemic growth induced by the tissue-specific pten mutations. Our data suggest a function for PINK1 in regulating systemic growth in Drosophila and shed light on its role in wasting in the context of PTEN mutations
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