Available online 17 February 2023, 106391
Author links open overlay panel, , ABSTRACTIn vivo control over metabolism is at the cutting edge of biomedical research. The particulars of mitochondrial function are especially important to understand in vivo to progress metabolic therapies that will be relevant for diseases of aging. Understanding the differences between how mitochondria function in vitro versus in vivo will be a necessary challenge to overcome to achieve mitochondrial medicine. In this article we outline how discoveries in invertebrate models will be informative for understanding the basic biology of mitochondria to streamline translation to mammals and eventually to humans. Further, we highlight examples of how what is known about mitochondria in vitro is translatable to in vivo models and, in some cases, to human diseases.
Section snippetsINTRODUCTIONMitochondria are evolutionarily ancient organelles that transform the chemical energy taken in from the environment (i.e. food) into usable energy for cells to function and thrive. This energy conversion happens through a potential energy intermediate that consists of a proton electrochemical gradient across the inner mitochondrial membrane called protonmotive force (PMF). PMF is created via oxidation of metabolites in the mitochondrial electron transport system (ETS), where redox reactions and
ConclusionOverall, we propose that the basic principles of bioenergetics first described in isolated mitochondria can be applied to in vivo models and can be explored further in the realm of basic biology using invertebrates (Fig. 1). These models can harness the power of cutting-edge technologies to inform mammalian in situ experiments to bridge the gap between isolated bioenergetics and human mitochondrial health. This gap must be bridged at the level of basic biology to effectively move laboratory
Author’s ContributionsBJB wrote and revised the manuscript, GP wrote and revised the manuscript, DJM provided critical feedback and revised the manuscript.
Conflicts of InterestThe authors declare there are no conflicts of interest to disclose.
ACKNOWLEDGEMENTSBJB and GP are supported by the Biological Mechanisms for Healthy Aging (BMHA) Training Grant NIH T32AG066574. Research and ideas contributing to this review were supported by P01 AG001751.
REFERENCES (51)P. MITCHELLCoupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanismNature
(1961)
P. Mitchell et al.Chemiosmotic hypothesis of oxidative phosphorylationNature
(1967)
S.W. PerryMitochondrial membrane potential probes and the proton gradient: a practical usage guideBiotechniques
(2011)
B.J. BerryOptogenetic control of mitochondrial protonmotive force to impact cellular stress resistanceEMBO Rep
(2020)
B.J. BerryNeuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance in C. elegansFASEB J
(2020)
H.M. HuangMitochondrial heterogeneity within and between different cell typesNeurochem Res
(2004)
D.M. WolfIndividual cristae within the same mitochondrion display different membrane potentials and are functionally independentEMBO J
(2019)
B. GlancyMitochondrial reticulum for cellular energy distribution in muscleNature
(2015)
B.J. Berry et al.Mitochondrial light switches: optogenetic approaches to control metabolismFEBS J
(2020)
Berry, B.J., et al., Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan. Nature...Berry, B., et al., Preservation of Mitochondrial Membrane Potential is Necessary for Lifespan Extension from Dietary...Ouyang Yeyun, et al., Phosphate Starvation Signaling Increases Mitochondrial Membrane Potential through...M. UlgheraitCircadian regulation of mitochondrial uncoupling and lifespanNat Commun
(2020)
M. PicardMitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibersAging Cell
(2010)
Y. SunLysosome activity is modulated by multiple longevity pathways and is important for lifespan extension inElife
(2020)
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