Mitochondria, energy, and metabolism in neuronal health and disease

Abstract

Mitochondria are associated with various cellular activities critical to homeostasis, particularly in the nervous system. The plastic architecture of the mitochondrial network and its dynamic structure play crucial roles in ensuring that varying energetic demands are rapidly met to maintain neuronal and axonal energy homeostasis. Recent evidence associates aging and neurodegeneration with anomalous neuronal metabolism as age‐dependent alterations of neuronal metabolism are now believed to occur prior to neurodegeneration. The brain has a high energy demand, which makes it particularly sensitive to mitochondrial dysfunction. Distinct cellular events causing oxidative stress or disruption of metabolism and mitochondrial homeostasis can trigger a neuropathology. This review explores the bioenergetic hypothesis for the neurodegenerative pathomechanisms, discussing factors leading to age‐related brain hypometabolism and its contribution to cognitive decline. Recent research on the mitochondrial network in healthy nervous system cells, its response to stress, and how it is affected by pathology, as well as current contributions to novel therapeutic approaches will be highlighted.

CERKL, a Retinal Dystrophy Gene, Regulates Mitochondrial Transport and Dynamics in Hippocampal Neurons

“…Correct mitochondrial function and dynamics are essential to maintain neuronal homeostasis and viability. In fact, in view of the high energy demand of the CNS, mitochondrial dysfunction is associated with the onset and progression of many neurodegenerative disorders [ 21 ]. Hence, in this work we aimed to assess CERKL implication on mitochondrial health in CNS tissues expressing Cerkl other than the retina, such as hippocampus.…”

Workshop on RanBP2/Nup358 and acute necrotizing encephalopathy

“…The link between RanBP2/Nup358 and mitochondrial function was further explored by Jomon Joseph (National centre for Cell Science, Pune, India). Impaired mitochondrial functions and autophagy have been implicated in many neurological disorders, possibly including ANE [ 107 , 108 ]. Joseph presented his lab work wherein he revealed that RanBP2/Nup358-positive annulate lamellae could often be present at ER-mitochondrial contact sites, which are hubs for regulation of various signaling pathways, intracellular calcium homeostasis, and autophagy [ 109 , 110 ].…”

Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain

“…Mitochondria play a crucial role in maintaining neuronal homeostasis by ensuring metabolic functions and energy production in the form of adenosine triphosphate (ATP), via oxidative phosphorylation (OXPHOS). [4] Moreover, mitochondria are essential to regulate multiple cellular processes, such as calcium homeostasis, ion channel activity and reactive oxygen species (ROS) signaling. [4] Deficits in mitochondrial functions are linked to chronic pain.…”

“…[4] Moreover, mitochondria are essential to regulate multiple cellular processes, such as calcium homeostasis, ion channel activity and reactive oxygen species (ROS) signaling. [4] Deficits in mitochondrial functions are linked to chronic pain. In humans, approximately 70% of the patients with heritable mitochondrial diseases have chronic pain.…”