Cell Reports Cover Article-Dr. Tao Wang’s lab discovers the mechanism of PINK1 in regulating cell growth

On March 28, 2021 ---- Dr. Tao Wang’s laboratory of National Institute of Biological Sciences, Beijing/Tsinghua Institute of Multidisciplinary Biomedical Research (TIMBR) published a new cover article titled “Roles of PINK1 in regulation of systemic growth inhibition induced by mutations of PTEN in Drosophila” online in Cell Reports. Researchers studied the mechanism of PINK1 in regulating cell growth in fruit fly, and revealed roles of PINK1 in regulation of systemic growth inhibition induced by mutations of PTEN.

Initially identified as a gene upregulated by the tumor suppressor PTEN (phosphatase and tensin homologue), PINK1 is expressed ubiquitously and imported into mitochondria. There is accumulating evidence that PINK1 kinase activity within healthy mitochondria helps to maintain mitochondrial oxidative phosphorylation and energy-producing functions. Therefore, in addition to its role in Parkin-mediated mitophagy, PINK1 regulates processes critical for cell survival, cell growth, and the progression of tumors. 
PTEN, one of the most frequently mutated genes in human cancers, is involved in the regulation of cell growth and cell proliferation by suppressing the Insulin Receptor (InR)/phosphoinositide-3-kinase (PI3K)/Akt pathway. The dramatic down-regulation of PINK1 in pten mutant cancer cells suggests that PINK1 functions as a tumor suppressor. In contast, PINK1 expression is elevated in some malignant tumors, suggesting pro-tumorigenic activity.
To solve the contradictory functions of PINK1 in tumor cell growth, we examined the role of PINK1 in regulating growth in Drosophila. Researchers demonstrate that pink1 deficiency resulted in multiple growth defects, and that PINK1 in mitochondria controlled cell growth independent of Parkin. Importantly, PINK1 regulated systemic growth in a cell non-autonomous manner, as loss of PINK1 in muscle cells resulted in ubiquitous reductions in cell growth and blocked systemic carbohydrate homeostasis and insulin signaling. This was mediated via the secreted insulin/IGF antagonist, ImpL2 (Imaginal morphogenesis protein-Late 2). These phenotypes resemble cachexia, in which tumors disrupt the growth of other cells and organs, causing tissue wasting in patients with advanced cancer. Indeed, a wasting-like syndrome was induced by loss of pten in multiple tissues, which was completely abolished by PINK1. This study suggests a new function for PINK1 in regulating systemic growth in Drosophila, and shed light on its role in wasting in context of PTEN mutations.
Yongchao Han, a postdoctoral fellow from Dr. Tao Wang’s lab is the first author of this article. Dr. Tao Wang is the corresponding author. The study was conducted at the National Institute of Biological Sciences, Beijing.

Full text link: https://doi.org/10.1016/j.celrep.2021.108875