This conceptual paper proposes an ontological reframing of cellular physiology by repositioning mitochondria as energy-governing agents rather than passive intracellular “power plants.” Challenging cell-centric models that treat cells as autonomous decision-makers, this work argues that cells function primarily as biological spaces where conditioned responses are expressed. Whether those responses occur at all depends on energetic permission governed by mitochondria, understood here as evolutionarily conserved microbial entities retained through endosymbiosis. By integrating insights from evolutionary biology, microbial ecology, mitochondrial physiology, and systems theory, this paper resolves persistent inconsistencies in modern physiology—such as cellular inactivity despite intact molecular machinery, failure of stimulation-based therapies, and metabolic collapse preceding disease. The framework aligns with Microbial Integration Architecture Theory (MIAT) and extracellular matrix–centric models, positioning energy governance as a prerequisite for cellular action, regeneration, and survival. This work does not present new experimental data, but offers a foundational conceptual clarification intended to support future empirical investigation.
Henny Hendiyani Irjanti (Tue,) studied this question.