Portal de investigación
Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition
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Autores de IBSAL
Autores ajenos a IBSAL
- Fernandez, E
- Carmeliet, P
Grupos
Abstract
Having direct access to brain vasculature, astrocytes can take up available blood nutrients and metabolize them to fulfil their own energy needs and deliver metabolic intermediates to local synapses(1,2). These glial cells should be, therefore, metabolically adaptable to swap different substrates. However, in vitro and in vivo studies consistently show that astrocytes are primarily glycolytic(3-7), suggesting glucose is their main metabolic precursor. Notably, transcriptomic data(8,9) and in vitro(10) studies reveal that mouse astrocytes are capable of mitochondrially oxidizing fatty acids and that they can detoxify excess neuronal-derived fatty acids in disease models(11,12). Still, the factual metabolic advantage of fatty acid use by astrocytes and its physiological impact on higher-order cerebral functions remain unknown. Here, we show that knockout of carnitine-palmitoyl transferase-1A (CPT1A)-a key enzyme of mitochondrial fatty acid oxidation-in adult mouse astrocytes causes cognitive impairment. Mechanistically, decreased fatty acid oxidation rewired astrocytic pyruvate metabolism to facilitate electron flux through a super-assembled mitochondrial respiratory chain, resulting in attenuation of reactive oxygen species formation. Thus, astrocytes naturally metabolize fatty acids to preserve the mitochondrial respiratory chain in an energetically inefficient disassembled conformation that secures signalling reactive oxygen species and sustains cognitive performance.
Datos de la publicación
- ISSN/ISSNe:
- 2522-5812, 2522-5812
- Tipo:
- Article
- Páginas:
- -
Nature Metabolism NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 30
Documentos
- No hay documentos
Filiaciones
Keywords
- CARNITINE PALMITOYLTRANSFERASE-I; BRAIN ENERGY-METABOLISM; NEURONAL-ACTIVITY; PROTEIN-KINASE; ASSOCIATION; CARBOXYLASE; GLYCOLYSIS; MECHANISM; TRANSPORT; ENZYME
Financiación
Proyectos asociados
Red de Enfermedades Vasculares Cerebrales (INVICTUS PLUS)
Investigador Principal: Ángeles Almeida Parra
RD16/0019/0018 . Instituto de Salud Carlos III . 2017
3. Frailty and Aging. 3.1. Healthy aging biological mechanisms oriented to the maintenance of functional autonomy and mechanisms leading to frailty and disability. CICERFES
Investigador Principal: Juan Pedro Bolaños Hernández
CB16/10/00282 . Instituto de Salud Carlos III . 2017
Red Temática de Excelencia de Investigación en Hipoxia (RedHYPOX)
Investigador Principal: Ángeles Almeida Parra
SAF2017-90794-REDT . Ministerio de Ciencia, Innovación y Universidades . 2018
Cita
Morant B,Jimenez D,Alonso P,Agulla J,Lapresa R,Garcia D,Yunta S,Lopez I,Fernandez E,Carmeliet P,Almeida A,Garcia M,Bolanos JP. Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition. Nat Metab. 2023. 5. (8):IF:18,900. (1).