Hyperpolarized mitochondria accumulate in Drosophila Hipk-overexpressing cells to drive tumor-like growth.

Journal of Cell Science
Kenneth Kin Lam WongEsther M Verheyen

Abstract

Both functional and dysfunctional mitochondria are known to underlie tumor progression. Here, we establish use of the proto-oncogene Drosophila Homeodomain-interacting protein kinase (Hipk) as a new tool to address this paradox. We find that, in Hipk-overexpressing tumor-like cells, mitochondria accumulate and switch from fragmented to highly fused interconnected morphologies. Moreover, elevated Hipk promotes mitochondrial membrane hyperpolarization. These mitochondrial changes are at least in part driven by the upregulation of Myc. Furthermore, we show that the altered mitochondrial energetics, but not morphology, is required for Hipk-induced tumor-like growth, because knockdown of pdsw (also known as nd-pdsw; NDUFB10 in mammals; a Complex I subunit) abrogates the growth. Knockdown of ATPsynβ (a Complex V subunit), which produces higher levels of reactive oxygen species (ROS) than pdsw knockdown, instead synergizes with Hipk to potentiate JNK activation and the downstream induction of matrix metalloproteinases. Accordingly, ATPsynβ knockdown suppresses Hipk-induced tumor-like growth only when ROS scavengers are co-expressed. Together, our work presents an in vivo tumor model featuring the accumulation of hyperfused and hyperpo...Continue Reading

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Citations

Jul 10, 2021·Disease Models & Mechanisms·Kenneth Kin Lam Wong, Esther M Verheyen

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Methods Mentioned

BETA
super-resolution microscopy
GTPases

Software Mentioned

ImageJ
Tophat
MiNA
Excel
SinCe
Mitochondrial Network Analysis ( MiNA )
Mito
MitoGraph
MiNA ( Mitochondrial Network Analysis )
BoxPlotR

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