Imperial College London

Dr Ana Lima

Faculty of MedicineNational Heart & Lung Institute

Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 2171a.lima14 Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

2 results found

Lima A, Burgstaller J, Sanchez Nieto JM, Rodriguez Tet al., 2017, The mitochondria and the regulation of cell fitness during earlymammalian development, Current Topics in Developmental Biology, Vol: 128, Pages: 339-363, ISSN: 0070-2153

From fertilization until the onset of gastrulation the early mammalian embryo undergoes a dramatic series of changes that converts a single fertilized cell into a remarkably complex organism. Much attention has been given to the molecular changes occurring during this process, but here we will review what is known about the changes affecting the mitochondria and how they impact on the energy metabolism and apoptotic response of the embryo. We will also focus on understanding what quality control mechanisms ensure optimal mitochondrial activity in the embryo, and in this way provide an overview of the importance of the mitochondria in determining cell fitness during early mammalian development.

Journal article

Willows R, Navaratnam N, Lima A, Read J, Carling Det al., 2017, Effect of different γ subunit isoforms on the regulation of AMPK, Biochemical Journal, Vol: 474, Pages: 1741-1754, ISSN: 1470-8728

AMP-activated protein kinase (AMPK) plays a key role in integrating metabolic pathways in response to energy demand. AMPK activation results in a wide range of downstream responses, many of which are associated with improved metabolic outcome, making AMPK an attractive target for the treatment of metabolic diseases. AMPK is a heterotrimeric complex consisting of a catalytic subunit (α) and two regulatory subunits (β and γ). The γ-subunit harbours the nucleotide-binding sites and plays an important role in AMPK regulation in response to cellular energy levels. In mammals, there are three isoforms of the γ-subunit and these respond differently to regulation by nucleotides, but there is limited information regarding their role in activation by small molecules. Here, we determined the effect of different γ-isoforms on AMPK by a direct activator, 991. In cells, 991 led to a greater activation of γ2-containing AMPK complexes compared with either γ1 or γ3. This effect was dependent on the long N-terminal region of the γ2-isoform. We were able to rule out an effect of Ser108 phosphorylation, since mutation of Ser108 to alanine in the β2-isoform had no effect on activation of AMPK by 991 in either γ1- or γ2-complexes. The rate of dephosphorylation of Thr172 was slower for γ2- compared with γ1-complexes, both in the absence and presence of 991. Our studies show that activation of AMPK by 991 depends on the nature of the γ-isoform. This finding may have implications for the design of isoform-selective AMPK activators.

Journal article

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