RT Journal
A1 Avolio, Rosario
A1 Agliarulo, Ilenia
A1 Criscuolo, Daniela
A1 Sarnataro, Daniela
A1 Auriemma, Margherita
A1 De Lella, Sabrina
A1 Pennacchio, Sara
A1 Calice, Giovanni
A1 Ng, Martin Y.
A1 Giorgi, Carlotta
A1 Pinton, Paolo
A1 Cooperman, Barry S.
A1 Landriscina, Matteo
A1 Esposito, Franca
A1 Matassa, Danilo Swann
T1 Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins
JF Genome Research 
JO Genome Research 
YR 2023 
FD August 01 
VO 33 
IS 8 
SP 1242 
OP 1257 
DO 10.1101/gr.277755.123 
UL http://genome.cshlp.org/content/33/8/1242.abstract 
AB A complex interplay between mRNA translation and cellular respiration has been recently unveiled, but its regulation in humans is poorly characterized in either health or disease. Cancer cells radically reshape both biosynthetic and bioenergetic pathways to sustain their aberrant growth rates. In this regard, we have shown that the molecular chaperone TRAP1 not only regulates the activity of respiratory complexes, behaving alternatively as an oncogene or a tumor suppressor, but also plays a concomitant moonlighting function in mRNA translation regulation. Herein, we identify the molecular mechanisms involved, showing that TRAP1 (1) binds both mitochondrial and cytosolic ribosomes, as well as translation elongation factors; (2) slows down translation elongation rate; and (3) favors localized translation in the proximity of mitochondria. We also provide evidence that TRAP1 is coexpressed in human tissues with the mitochondrial translational machinery, which is responsible for the synthesis of respiratory complex proteins. Altogether, our results show an unprecedented level of complexity in the regulation of cancer cell metabolism, strongly suggesting the existence of a tight feedback loop between protein synthesis and energy metabolism, based on the demonstration that a single molecular chaperone plays a role in both mitochondrial and cytosolic translation, as well as in mitochondrial respiration.