Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation DuringDrosophilaDevelopment

Abstract

Cell proliferation and tissue growth depend on the coordinated regulation of multiple signaling molecules and pathways during animal development. Previous studies have linked mitochondrial function and the Hippo signaling pathway in growth control. However, the underlying molecular mechanisms are not fully understood. Here we identify a Drosophila mitochondrial inner membrane protein ChChd3 as a novel regulator for tissue growth. Loss of ChChd3 leads to tissue undergrowth and cell proliferation defects. ChChd3 is required for mitochondrial fusion and removal of ChChd3 increases mitochondrial fragmentation. ChChd3 is another mitochondrial target of the Hippo pathway, although it is only partially required for Hippo pathway-mediated overgrowth. Interestingly, lack of ChChd3 leads to inactivation of Hippo activity under normal development, which is also dependent on the transcriptional coactivator Yorkie (Yki). Furthermore, loss of ChChd3 induces oxidative stress and activates the JNK pathway. In addition, depletion of other mitochondrial fusion components, Opa1 or Marf, inactivates the Hippo pathway as well. Taken together, we propose that there is a cross-talk between mitochondrial fusion and the Hippo pathway, which is essential in controlling cell proliferation and tissue homeostasis in Drosophila.

Molecular Features of the YAP Inhibitor Verteporfin: Synthesis of Hexasubstituted Dipyrrins as Potential Inhibitors of YAP/TAZ, the Downstream Effectors of the Hippo Pathway

“…VP, which is mainly localized in the mitochondria, might also affect YAP and TAZ expression through mitochondrial fusion/Hippo pathway cross‐talk . This link between the Hippo pathway and mitochondrial fusion could be of significance to cancer biology …”

“…[33] This link between the Hippop athway and mitochondrial fusion could be of significance to cancer biology. [34] Experimental Section Biology Human breast cancer cell line:T he MDA-MB-231 cell line was purchased from the American Type Culture Collection (ATCC) and cultivated in DMEM media containing 10 %h eat-inactivated fetal bovine serum (FBS), l-glutamine (2 mm), and penicillin/streptomycin (100 UmL À1 /0.1 mg mL À1 ).…”

Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss

“…UAS ‐ RNAi lines against marf (BL55189) and drp1 (BL51483) were obtained from the Bloomington Drosophila Stock Center (BL). The efficiencies were described previously (Deng et al, 2016; Smith et al, 2019) and were tested again in this study (Figure ). The nos ‐ Vp16 ‐ GAL4 line was used to drive RNAi expression in the germline line (Doren, Williamson, & Lehmann, 1998; Tseng et al, 2014).…”

Sub-mitochondrial localization of the genetic-tagged mitochondrial intermembrane space-bridging components Mic19, Mic60 and Sam50

“…However, it was recently found that Mic19 and Mic60 are involved with Parkin recruitment to mitochondria and this Parkin translocation is controlled by PKA-mediated phosphorylation (Akabane et al, 2016), suggesting that these proteins have a role in the protection of mitochondria with low membrane potential from selective autophagy in neurons. Finally, it was recently reported that Mic19 is part of the Hippo pathway in Drosophila development (Deng et al, 2016) promoting mitochondrial fusion and biogenesis by activating mitochondrial genes. In the bigger picture, this pathway is a signaling cascade that controls tissue growth and apoptosis.…”