Mitoception via the Metabokine GDF15 and Human Health.

Area of Science:

• Cellular biology
• Neuroscience
• Metabolic regulation

Background:

• Organisms require precise control of cellular energy metabolism for survival.
• Metaboception, a brain-directed process, monitors metabolic energy states.
• Growth Differentiation Factor 15 (GDF15) is identified as a key mediator in a specific metaboceptive pathway.

Purpose of the Study:

• To review evidence for the GDF15-mediated signaling cascade, termed mitoception.
• To introduce the psychobiology of GDF15 and its role in cellular energy homeostasis.
• To propose a GDF15-driven mitoception cascade model and its implications.

Main Methods:

• Review of existing scientific literature on GDF15, cellular stress, and interoception.
• Analysis of the afferent and efferent signaling arms of the proposed mitoception cascade.
• Integration of GDF15's role in cellular energy balance and systemic responses.

Main Results:

• Mitoception involves an afferent arm where cellular stress triggers GDF15 release due to an energy gap.
• An efferent arm is initiated when GDF15 signals brainstem receptors, causing fatigue, anxiety, and neuroendocrine responses.
• GDF15 signaling promotes systemic energy conservation and fuel mobilization.

Conclusions:

• The GDF15-mitoception cascade links cellular energy status to psychological and physiological stress responses.
• This pathway influences allostasis, survival, and long-term health.
• Understanding GDF15 psychobiology offers insights into disease risk, mental health, mood, resilience, well-being, and aging.