1. Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS).
- Author
-
Larrea D, Tamucci KA, Kabra K, Velasco KR, Yun TD, Pera M, Montesinos J, Agrawal RR, Paradas C, Smerdon JW, Lowry ER, Stepanova A, Yoval-Sanchez B, Galkin A, Wichterle H, and Area-Gomez E
- Subjects
- Humans, Animals, Spinal Cord metabolism, Mice, Glucose metabolism, Fatty Acids metabolism, Male, Energy Metabolism, Pyruvic Acid metabolism, Intracellular Membranes metabolism, Electron Transport Complex I metabolism, Electron Transport Complex I genetics, Brain metabolism, Mitochondria Associated Membranes, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis genetics, Endoplasmic Reticulum metabolism, Mitochondria metabolism
- Abstract
Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here that this impairment in the crosstalk between mitochondria and the ER impedes the use of glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids to sustain energy production. Over time, this deficiency alters mitochondrial electron flow and the active/dormant status of complex I in spinal cord tissues, but not in the brain. These findings suggest mitochondria-associated ER membranes (MAM domains) play a crucial role in regulating cellular glucose metabolism and that MAM dysfunction may underlie the bioenergetic deficits observed in ALS., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
- Published
- 2025
- Full Text
- View/download PDF