Regulation of neuron mitochondrial biogenesis and relevance to brain health

Abstract

Mitochondrial dysfunction has severe cellular consequences, and is linked to aging and neurological disorders in humans. Impaired energy supply or Ca(2+) buffering, increased ROS production, or control of apoptosis by mitochondria may contribute to the progressive decline of long-lived postmitotic cells. Mitochondrial biogenesis refers to the process via which cells increase their individual mitochondrial mass. Mitochondrial biogenesis may represent an attempt by cells to increase their aerobic set point, or an attempt to maintain a pre-existing aerobic set point in the face of declining mitochondrial function. Neuronal mitochondrial biogenesis itself has been poorly studied, but investigations from other tissues and model systems suggest a series of transcription factors, transcription co-activators, and signal transduction proteins should function to regulate mitochondrial number and mass within neurons. We review data pertinent to the mitochondrial biogenesis field, and discuss implications for brain aging and neurodegenerative disease research efforts.

Mitochondrial Quality Control as a Therapeutic Target

“…The unique challenge for the cell is the rapid synchronization of mtDNA replication and mitochondrial-encoded gene expression in conjunction with the upregulation of many genes for NEMPs and associated subsets of nonmitochondrial genes. Subsequently, it became known that the program is activated by changes in substrate availability (e.g., starvation) (Moreno-Loshuertos et al, 2006 and by certain paracrine effectors and hormones (Scarpulla, 2011) necessary for the cell to maintain its functional mitochondrial mass (Onyango et al, 2010). The process is also essential to recovery from oxidative stress, inflammation, and mitochondrial drug toxicity (Suliman et al, 2007a).…”

Senescence-Accelerated Mice P8: A Tool to Study Brain Aging and Alzheimer's Disease in a Mouse Model

“…This raises the possibility that switching from an enhanced state to a diminished state of mitochondrial biogenesis could represent a key transition between normal brain aging and AD. If so, then the induction of mitochondrial biogenesis should be a viable pharmacologic target for the treatment of AD and other neurodegenerative diseases (for a review, [122]). …”

Prevention of Epilepsy by Low-Dose Artesunate + Esomeprazole-Furosemide Sequential Therapy.

“…This effect may largely be explained by these agents upregulating mitochondrial biogenesis. [60][61] [62] The issue of drug resistance by alterations in GABA-A receptor and increased MDR especially in temporal lobe epilepsy may also be significantly addressed by this sequential drug combination therapy. [62][63] For example, artesunate and the PPIs may inhibit P-glycoprotein (P-gp) or multi-drug resistance protein-I.…”