Title (eng)
The Mysteries of LETM1 Pleiotropy
Abstract (eng)
LETM1 is a nuclear-encoded protein located in the inner mitochondrial membrane, playing a critical role in regulating mitochondrial cation and volume homeostasis. However, numerous studies on functional features, molecular interactions, and disease-associated effects of LETM1 revealed that LETM1 is also involved in other metabolic functions including glucose utilization, mitochondrial DNA and ribosome organization, cristae architecture and respiratory complex stability. Undisputedly, osmoregulatory processes are essential for mitochondrial functionality, but the pleiotropic aspects of LETM1 challenges us to understand the core function of LETM1, which still remains elusive. In this review, we provide an overview of the current knowledge and latest developments regarding the activities involving LETM1. We highlight various findings that offer different functional perspectives and ideas on the core function of LETM1. Specifically, we emphasize data supporting LETM1's role as a mitochondrial translational factor, K+/H+ exchanger, or Ca2+/H+ exchanger, along with recent findings on its interaction with ATAD3A and TMBIM5. We also present the severe clinical implications of LETM1 deficiency. Finally, we discuss emerging questions raised by the different views on LETM1, which need to be addressed to guide future research directions and ultimately resolve the function of this essential protein and develop targeted therapeutic strategies.
Keywords (eng)
HumansAnimalsMitochondria MetabolismMitochondria GeneticsMitochondrial Proteins MetabolismMitochondrial Proteins GeneticsMembrane Proteins MetabolismMembrane Proteins GeneticsGenetic PleiotropyCalcium-Binding Proteins
Type (eng)
Language
[eng]
Persistent identifier
Is in series
Title (eng)
Pharmacological Research
Volume
210
ISSN
1096-1186
Issued
2024
Number of pages
8
Publication
Elsevier
Version type (eng)
Date issued
2024
Access rights (eng)
License
Rights statement (eng)
© 2024 The Authors
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DOI
https://phaidra.vetmeduni.ac.at/o:3836
https://doi.org/10.1016/j.phrs.2024.107485 - Content
- DetailsObject typePDFDocumentFormatapplication/pdfCreated31.01.2025 10:03:51 UTC
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