Regulation of Mitochondrial Energy Metabolism

Abstract

Mitochondria are organelles that play various roles in the physiology processes such as energy production, calcium signalling and apoptosis. Mitochondria are continually solicited to reply to the cell's energy demand. Thus, impairments in mitochondrial function can lead to diseases, because of its implication into cells homeostasis and its essential role in ATP (adenosine triphosphate) production. The energy metabolism is regulated by mTOR (mechanistic target of rapamycin) and AMPK (AMP‐activated protein kinase) signalling pathways. In addition, the mitochondrial biogenesis is controlled by a triad of transcription factors, PGC1α (PPARγ coactivator 1 alpha)–NRF1 (nuclear respiratory factor 1)–TFAM (mitochondrial transcription factor A). Once the regulations behind the energy synthesis are altered, the organelle will adapt accordingly. Overall, the deficiencies that characterised mitochondria in pathologies are not just about structural defaults. Impairments can target regulation processes. In other words, the energy remodelling or worse, the mitochondrial energy crisis, results from upstream factors. Then, the mechanisms behind regulations of mitochondrial energy metabolism appear to impact cell physiology, as can be deduced from remodelling reported in neurodegenerative diseases or even cancer.

Key Concepts

  • ROS are involved in energy homeostasis by activating AMPK.
  • PGC1á is not only related to mitochondrial biogenesis. It stimulates gluconeogenesis.
  • MFN2 may have opposite functions in neurodegenerative disease and cancer.
  • Mitochondrial deficiencies that induce impairments in energy production, lead to neurodegeneration.
  • Bioenergetics characterization of tumours is essential for specific targeting in chemotherapy treatment.
  • LONP1, involved in mitochondrial quality control and energy metabolism, may be consider as a bioenergetic biomarker in cancer.
  • AMPK induces mitochondrial biogenesis and catabolism; while mTORC1 induces anabolism.

Keywords: bioenergetics; metabolism; mitochondria; regulation; signalling

Figure 1. Yin and yang of bioenergetics regulation. mTORC1, activated in the presence of high levels of amino acids and nutrients, can stimulate macromolecules synthesis, energy consumption or cell growth. AMPK induces ATP production via the ETC and is activated by a high AMP/ATP ratio (diet and physical activity). The two main metabolic sensors work in antagonist manners to block (AMPK) or promote (mTOR) autophagy which consist in regulated degradation of complex molecules to produce basic components which will be used in energy production or other metabolic pathways.
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Lalou, Claude, and Bellance, Nadège(Apr 2018) Regulation of Mitochondrial Energy Metabolism. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027837]