Review

Cellular and Molecular Life Sciences

, Volume 66, Issue 15, pp 2427-2443

Intracellular protein degradation in mammalian cells: recent developments

  • Erwin KnechtAffiliated withCentro de Investigación Príncipe FelipeCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII Email author 
  • , Carmen AguadoAffiliated withCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII
  • , Jaime CárcelAffiliated withCentro de Investigación Príncipe Felipe
  • , Inmaculada EstebanAffiliated withCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII
  • , Juan Miguel EsteveAffiliated withCentro de Investigación Príncipe Felipe
  • , Ghita GhislatAffiliated withCentro de Investigación Príncipe Felipe
  • , José Félix MorunoAffiliated withCentro de Investigación Príncipe Felipe
  • , José Manuel VidalAffiliated withCentro de Investigación Príncipe Felipe
  • , Rosana SáezAffiliated withDepartamento de Biología Celular, Universidad de Valencia

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Abstract

In higher organisms, dietary proteins are broken down into amino acids within the digestive tract but outside the cells, which incorporate the resulting amino acids into their metabolism. However, under certain conditions, an organism loses more nitrogen than is assimilated in the diet. This additional loss was found in the past century to come from intracellular proteins and started an intensive research that produced an enormous expansion of the field and a dispersed literature. Therefore, our purpose is to provide an updated summary of the current knowledge on the proteolytic machinery involved in intracellular protein degradation and its physiological and pathological relevance, especially addressed to newcomers in the field who may find further details in more specialized reviews. However, even providing a general overview, this is an extremely wide field and, therefore, we mainly focus on mammalian cells, while other cells will be mentioned only for comparison purposes.

Keywords

Intracellular protein degradation Proteases Proteasomes Ubiquitin Lysosomes Autophagy Cell injury