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Study Unveils Fat Transport Deficiency as Key Factor in Rare Childhood Metabolic Crises - Video

Published On 2025-03-04T08:00:00+05:30  |  Updated On 4 March 2025 8:00 AM IST
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Overview

Researchers studying a protein linked to a rare, severe disease have made a discovery that sheds light on how cells meet their energy needs during a severe metabolic crisis. The findings could lead to new treatments for the disease and open new avenues of research for other conditions involving impaired fat metabolism.
Scientists at the Centre for Genomic Regulation (CRG) in Barcelona first identified a handful of protein-coding genes called TANGO in 2006. In 2016, the researchers found that mutations in TANGO2 causes a rare disease now officially recognised as TANGO2 Deficiency Disorder (TDD).
In the latest study, published in the Journal of Cell Biology, the researchers demonstrate that TANGO2 directly binds to a key fat molecule called acyl-CoA, transporting them like a shuttle inside cells. The authors of the study made the findings by tagging TANGO2 with glowing markers to trace its movements in live cells.
“Families sometimes only find out their child has TANGO2 deficiency only after a dramatic incident,” says ICREA Research Professor Vivek Malhotra, senior author of the study who first discovered the TANGO family of genes two decades ago. “One moment, everything seems normal. Then, under an energy-demanding situation, these children’s muscles and hearts fail to keep up.”
One of the few existing treatments for the condition involves giving patients high doses of Vitamin B5, an essential nutrient known to generate Coenzyme A
Though TANGO2 deficiency is rare, the science behind how cells shuttle fat to fuel-hungry tissues might apply more broadly. “It could help us understand heart or muscle diseases in the general population,” says Dr. Malhotra. “Millions of people wrestle with heart problems or abnormal fat metabolism, and the fundamental chemistry isn’t all that different. The biology of rare diseases can help us understand human health in general.”
Ref: Agustin Leonardo Lujan, Ombretta Foresti, Jose Wojnacki, Gonzalo Bigliani, Nathalie Brouwers, Maria Jesus Pena, Stefania Androulaki, Tomomi Hashidate-Yoshida, Maria Kalyukina, Sergey S. Novoselov, Hideo Shindou, Vivek Malhotra; TANGO2 is an acyl-CoA binding protein. J Cell Biol 5 May 2025; 224 (5): e202410001. doi: https://doi.org/10.1083/jcb.202410001

Speakers

Dr. Bhumika Maikhuri

BDS, MDS

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