The germline coordinates mitokine signaling, 2024, Shen et al.

The germline coordinates mitokine signaling
Koning Shen; Jenni Durieux; Cesar G. Mena; Brant M. Webster; C. Kimberly Tsui; Hanlin Zhang; Larry Joe; Kristen M. Berendzen; Andrew Dillin

The ability of mitochondria to coordinate stress responses across tissues is critical for health. In C. elegans, neurons experiencing mitochondrial stress elicit an inter-tissue signaling pathway through the release of mitokine signals, such as serotonin or the Wnt ligand EGL-20, which activate the mitochondrial unfolded protein response (UPRMT) in the periphery to promote organismal health and lifespan.

We find that germline mitochondria play a surprising role in neuron-to-periphery UPRMT signaling. Specifically, we find that germline mitochondria signal downstream of neuronal mitokines, Wnt and serotonin, and upstream of lipid metabolic pathways in the periphery to regulate UPRMT activation. We also find that the germline tissue itself is essential for UPRMT signaling.

We propose that the germline has a central signaling role in coordinating mitochondrial stress responses across tissues, and germline mitochondria play a defining role in this coordination because of their inherent roles in germline integrity and inter-tissue signaling.

HIGHLIGHTS

• A germline mitochondrial gene ucr-2.3 is required for cell non-autonomous UPRMT
• The germline and germline mitochondria are also required for cell non-autonomous UPRMT
• Germline mitochondria control intestinal UPRMT downstream of neuronal mitokines
• The germline regulates intestinal UPRMT through lipid synthesis and transport pathways


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