Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine.

Nature Communications
Kerui HuangHua Bai

Abstract

Aging is characterized by a chronic, low-grade inflammation, which is a major risk factor for cardiovascular diseases. It remains poorly understood whether pro-inflammatory factors released from non-cardiac tissues contribute to the non-autonomous regulation of age-related cardiac dysfunction. Here, we report that age-dependent induction of cytokine unpaired 3 (upd3) in Drosophila oenocytes (hepatocyte-like cells) is the primary non-autonomous mechanism for cardiac aging. We show that upd3 is significantly up-regulated in aged oenocytes. Oenocyte-specific knockdown of upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. We term hormonal factors induced by peroxisome dysfunction as peroxikines. Intriguingly, oenocyte-specific overexpression of Pex5, the key peroxisomal import receptor, blocks age-related upd3 induction and alleviates cardiac arrhythmicity. Thus, our studies identify an important role of hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.

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Citations

Sep 29, 2020·Frontiers in Cell and Developmental Biology·C PridieAndrew J Simmonds
Aug 19, 2021·Cell Reports·Guangming DingWei Song
Dec 12, 2021·The FEBS Journal·Alessandro Filosa, Suphansa Sawamiphak

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Methods Mentioned

BETA
RNA-Seq
Assay
Fluorescence

Software Mentioned

Olympus CellSens Dimension
GeneSwitch
GraphPad
HCI
MATLAB
SOHA
GraphPad Prism
CellSens

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