Is REDD1 a metabolic double agent? Lessons from physiology and pathology

The Akt/mechanistic target of rapamycin (mTOR) signaling pathway governs macromolecule synthesis, cell growth, and metabolism in response to nutrients and growth factors. Regulated in development and DNA damage response (REDD)1 is a conserved and ubiquitous protein, which is transiently induced in r...

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Published in:	American Journal of Physiology: Cell Physiology 2020-11, Vol.319 (5), p.C807-C824
Main Authors:	Britto, Florian A, Dumas, Karine, Giorgetti-Peraldi, Sophie, Ollendorff, Vincent, Favier, François B
Format:	Article
Language:	eng
Subjects:	AKT protein Apoptosis Apoptosis - genetics Cell growth Depression - genetics Depression - metabolism Depression - pathology Diabetes mellitus Diabetes Mellitus - genetics Diabetes Mellitus - metabolism Diabetes Mellitus - pathology DNA damage Gene Expression Regulation Growth factors Humans Inflammatory diseases Life Sciences Metabolism Mitochondria Mitochondria - metabolism Mitochondria - pathology Muscle Weakness - genetics Muscle Weakness - metabolism Muscle Weakness - pathology Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Neurodegenerative diseases Neurodegenerative Diseases - genetics Neurodegenerative Diseases - metabolism Neurodegenerative Diseases - pathology Nutrients Obesity - genetics Obesity - metabolism Obesity - pathology Oxidative stress Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Rapamycin Reactive oxygen species Reactive Oxygen Species - metabolism Signal Transduction Stress, Physiological - genetics TOR protein TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism Transcription Factors - genetics Transcription Factors - metabolism
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Summary:	The Akt/mechanistic target of rapamycin (mTOR) signaling pathway governs macromolecule synthesis, cell growth, and metabolism in response to nutrients and growth factors. Regulated in development and DNA damage response (REDD)1 is a conserved and ubiquitous protein, which is transiently induced in response to multiple stimuli. Acting like an endogenous inhibitor of the Akt/mTOR signaling pathway, REDD1 protein has been shown to regulate cell growth, mitochondrial function, oxidative stress, and apoptosis. Recent studies also indicate that timely REDD1 expression limits Akt/mTOR-dependent synthesis processes to spare energy during metabolic stresses, avoiding energy collapse and detrimental consequences. In contrast to this beneficial role for metabolic adaptation, REDD1 chronic expression appears involved in the pathogenesis of several diseases. Indeed, REDD1 expression is found as an early biomarker in many pathologies including inflammatory diseases, cancer, neurodegenerative disorders, depression, diabetes, and obesity. Moreover, prolonged REDD1 expression is associated with cell apoptosis, excessive reactive oxygen species (ROS) production, and inflammation activation leading to tissue damage. In this review, we decipher several mechanisms that make REDD1 a likely metabolic double agent depending on its duration of expression in different physiological and pathological contexts. We also discuss the role played by REDD1 in the cross talk between the Akt/mTOR signaling pathway and the energetic metabolism.
ISSN:	0363-6143 1522-1563