TY - JOUR
T1 - Mitochondrial Biogenesis as a Pharmacological Target
T2 - A New Approach to Acute and Chronic Diseases
AU - Whitaker, Ryan M.
AU - Corum, Daniel
AU - Beeson, Craig C.
AU - Schnellmann, Rick G.
N1 - Funding Information:
The authors acknowledge support from the NIH [R01 GM084147 (R.G.S.) and F30 DK096964 (R.M.W.)] and the US Department of Veterans Affairs [1BX000851 (R.G.S.)].
Publisher Copyright:
Copyright © 2016 by Annual Reviews. All rights reserved.
PY - 2016/1/6
Y1 - 2016/1/6
N2 - Mitochondrial dysfunction is a key pathophysiological component of many acute and chronic diseases. Maintenance of mitochondrial homeostasis through the balance of mitochondrial turnover, fission and fusion, and generation of new mitochondria via mitochondrial biogenesis is critical for tissue health. Pharmacological activation of mitochondrial biogenesis can enhance oxidative metabolism and tissue bioenergetics, and improve organ function in conditions characterized by mitochondrial dysfunction. However, owing to the complexity of mitochondrial assembly and maintenance, identification of specific activators of mitochondrial biogenesis has been difficult. This review provides an overview of the role of mitochondrial dysfunction in acute and chronic diseases, details the current state of therapeutics for the stimulation of mitochondrial biogenesis and their effects on disease outcomes, describes new screening methodologies to identify novel stimulators and noncanonical pathways of mitochondrial biogenesis, and discusses potential hurdles of mitochondrial biogenesis as a therapeutic strategy.
AB - Mitochondrial dysfunction is a key pathophysiological component of many acute and chronic diseases. Maintenance of mitochondrial homeostasis through the balance of mitochondrial turnover, fission and fusion, and generation of new mitochondria via mitochondrial biogenesis is critical for tissue health. Pharmacological activation of mitochondrial biogenesis can enhance oxidative metabolism and tissue bioenergetics, and improve organ function in conditions characterized by mitochondrial dysfunction. However, owing to the complexity of mitochondrial assembly and maintenance, identification of specific activators of mitochondrial biogenesis has been difficult. This review provides an overview of the role of mitochondrial dysfunction in acute and chronic diseases, details the current state of therapeutics for the stimulation of mitochondrial biogenesis and their effects on disease outcomes, describes new screening methodologies to identify novel stimulators and noncanonical pathways of mitochondrial biogenesis, and discusses potential hurdles of mitochondrial biogenesis as a therapeutic strategy.
KW - Drug screening
KW - High-throughput respirometry
KW - Mitochondrial homeostasis
KW - Tissue bioenergetics
UR - http://www.scopus.com/inward/record.url?scp=84954116598&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954116598&partnerID=8YFLogxK
U2 - 10.1146/annurev-pharmtox-010715-103155
DO - 10.1146/annurev-pharmtox-010715-103155
M3 - Article
C2 - 26566156
AN - SCOPUS:84954116598
SN - 0362-1642
VL - 56
SP - 229
EP - 249
JO - Annual review of pharmacology and toxicology
JF - Annual review of pharmacology and toxicology
ER -