Hakuna MAM-Tata: Investigating the role of mitochondrial-associated membranes in ALS
| Autor: | Anna Fernàndez Bernal, Natàlia Mota, Reinald Pamplona, Estela Area-Gomez, Manuel Portero-Otin |
|---|---|
| Přispěvatelé: | Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Generalitat de Catalunya, Fundela, RedELA Investigación, Fundació Miquel Valls, European Commission, Fernández Bernal, Anna, Pamplona, Reinald, Area-Gomez, Estela, Portero-Otín, Manuel |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Popis: | 10 p.-7 fig. Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease leading to selective and progressive motor neuron (MN) death. Despite significant heterogeneity in pathogenic and clinical terms, MN demise ultimately unifies patients. Across the many disturbances in neuronal biology present in the disease and its models, two common trends are loss of calcium homeostasis and dysregulations in lipid metabolism. Since both mitochondria and endoplasmic reticulum (ER) are essential in these functions, their intertwin through the so-called mitochondrial-associated membranes (MAMs) should be relevant in this disease. In this review, we present a short overview of MAMs functional aspects and how its dysfunction could explain a substantial part of the cellular disarrangements in ALS's natural history. MAMs are hubs for lipid synthesis, integrating glycerophospholipids, sphingolipids, and cholesteryl ester metabolism. These lipids are essential for membrane biology, so there should be a close coupling to cellular energy demands, a role that MAMs may partially fulfill. Not surprisingly, MAMs are also host part of calcium signaling to mitochondria, so their impairment could lead to mitochondrial dysfunction, affecting oxidative phosphorylation and enhancing the vulnerability of MNs. We present data supporting that MAMs' maladaptation could be essential to MNs' vulnerability in ALS. Grants were received from the Instituto de Salud Carlos III (PI 17-000134, PI 20-0155) to MPO, from the Ministerio de Ciencia e Innovación (PID2021-126818NB-I00) and Project ALS to EAG, and from the Generalitat de Catalunya 2017SGR696 to RP. Support was also received in the form of a FUNDELA Grant, RedELA-Plataforma Investigación and the Fundació Miquel Valls (Jack Van den Hoek donation).FEDER funds are acknowledged (“A way to make Europe”). These funding bodies had no roles in the design of the study and collection,analysis, and interpretation of data and in writing the manuscript. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|