8 Chapter 1 FATTY ACID METABOLISM Fatty acids are important molecules with multiple roles, such as structural components of cell membranes, nutrients and signaling molecules1. They can be stored as triglycerides to be used during extended periods of fasting, illness or exercise. Fatty acid oxidation (FAO) provides a large amount of the energy requirements during periods when glucose and gluconeogenic precursors are depleted. FAO is a key metabolic process for human physiology, and its importance is highlighted by the number of inherited disorders caused by defects in the pathway2. While the majority of fatty acids are oxidized via mitochondrial β-oxidation, peroxisomes also play a key role in FAO of different substrates. Interestingly, these two organelles are able to communicate and interact with each other in the oxidation of fatty acids. Organelles involved in metabolism of fatty acids Mitochondria Mitochondria are subcellular organelles in charge of the bulk of fatty-acid oxidation. These double-membrane organelles are in charge of the production of the majority of the ATP in the cell through oxidative phosphorylation3. Amongst many of the functions of mitochondria I could highlight energy metabolism, redox metabolism, calcium regulation, and signaling 4. Regarding fatty acid metabolism, mitochondria are in charge of oxidizing long- to short-chain fatty acids to produce ATP under catabolic conditions. To do so, mitochondria can perform β-oxidation of fatty acids, a cyclic process that leads to the production of acetyl-CoA and NADH and FADH2 2. These products are further metabolized in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation where ATP is formed. Mitochondria are highly dynamic organelles, which continuously experience processes of recycling and reshaping5,6. They are also able to respond to their environment regulating both their structure and function. Defects in mitochondrial metabolism, namely inherited defects, DNA damage during aging and environmental factors, such as diet can be detrimental for cell survival7. Peroxisomes Peroxisomes are small (0.1–1 µm), single-membrane subcellular organelles found in most eukaryotic cells. These organelles exert a wide range of metabolic
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