Lipid droplets (LDs), initially considered “inert” lipid deposits, have gained during the last decade the classification of cytosolic organelles due to their defined composition and the multiplicity of specific cellular functions in which they are involved. The classification of LD as organelles brings along the need for their regulated turnover and recent findings support the direct contribution of autophagy to this turnover through a process now described as lipophagy. This paper focuses on the characteristics of this new type of selective autophagy and the cellular consequences of the mobilization of intracellular lipids through this process. Lipophagy impacts the cellular energetic balance directly, through lipid breakdown and, indirectly, by regulating food intake. Defective lipophagy has been already linked to important metabolic disorders such as fatty liver, obesity and atherosclerosis, and the age-dependent decrease in autophagy could underline the basis for the metabolic syndrome of aging. 1. Introduction Autophagy, or the process of degradation of intracellular components in lysosomes, has been traditionally linked to cellular energy balance and to the cellular nutritional status [1, 2]. In fact, although during the recent revival of the autophagic process, most of the emphasis has been placed on its role in other cellular functions such as cellular quality control, remodeling, or cell defense, the first descriptions of the autophagic process in the early 1960s already stated that conditions such as starvation lead to its activation [3–5]. These early studies proposed that autophagic activation during starvation was necessary to maintain the cellular energetic balance. Later studies in yeast, in fact confirmed that activation of autophagy was essential to preserve cellular viability during nutritional starvation (nitrogen depletion in yeast), and that mutants defective in autophagy were lethal [6, 7]. In most of these studies emphasis was placed on the ability of autophagy to supply through degradation of protein products the amino acids required to maintain protein synthesis under the extreme nutritional conditions. However, the contribution of autophagy to the cellular energetic balance may not be solely dependent on this capacity to provide free amino acids, which in fact, are a relatively inefficient source of energy when oxidized to urea and carbon dioxide. Recent studies support that autophagy can also provide energetically more efficient essential components, such as free fatty acids (FFAs) and sugars. In this paper, we focus on the
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