Causes of differences in respiration rate of hepatocytes from mammals of different body mass.
Abstract: Resting O2 consumption of hepatocytes isolated from mammals ranging in mass from 20-g mice to 200-kg horses decreases with increasing body mass. The substrate oxidation system increases in activity with increasing body mass and mitochondrial proton leak and phosphorylation system decrease in activity, resulting in a higher mitochondrial membrane potential in hepatocytes from larger mammals. The absolute rates of O2 consumption due to nonmitochondrial processes, substrate oxidation, mitochondrial proton leak, and the phosphorylation system decrease with increasing body mass. These decreases are due partly to a decrease in mitochondrial number per cell and partly to decrease in mitochondrial inner membrane proton leakiness and in ATP turnover by cells from larger mammals. Quantitatively, the proportion of total cell O2 consumption by nonmitochondrial processes (13%) and oxidation of substrates (87%) and the proportions used to drive mitochondrial proton leak (19%) and the phosphorylation system (68%) are the same for hepatocytes from all mammals investigated. The effect of matched decreases in the rates of proton leak and of ATP turnover is to keep the effective amount of ATP synthesized per unit of O2 consumed relatively constant with body mass, suggesting that the observed value is optimal.
Publication Date: 1995-11-01 PubMed ID: 7503313DOI: 10.1152/ajpregu.1995.269.5.R1213Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research study explores why the rate of respiration of liver cells, or hepatocytes, differs among mammals of varying body sizes. The study found that the resting oxygen consumption of these cells decreases as the body mass of the mammal increases.
The Findings
- The research presented various results surrounding the cellular respiration of hepatocytes derived from a diverse array of mammals, ranging from 20-gram mice to 200-kilogram horses.
- Primarily, the study found that resting oxygen (O2) consumption in these cells decreases correspondingly with an increase in the body mass of the mammal. This means that larger mammals utilise less oxygen in the resting state of their hepatocytes.
- In relation to this, the study also observed a rise in the activity of the substrate oxidation system as the body mass increases.
- Simultaneously, the mitochondrial proton leak and phosphorylation system exhibited reduced activity, which led to a higher mitochondrial membrane potential in hepatocytes from larger mammals.
The Role of Mitochondrial Components
- A key finding is that the absolute rates of O2 consumption due to non-mitochondrial processes, substrate oxidation, mitochondrial proton leak, and the phosphorylation system all decreased as the mammal’s body mass increased.
- These reductions are attributed to both a decrease in the number of mitochondria per cell and a decrease in the leakiness of protons across the mitochondrial inner membrane, along with a reduction in ATP turnover in cells from larger mammals.
Consistency Across Body Masses
- Quantitatively, the researchers noted that the proportions of total cell O2 consumption remained consistent across the various mammals, regardless of their body mass.
- These proportions were found to be divided into non-mitochondrial processes (13%) and oxidation of substrates (87%), with the O2 used to drive mitochondrial proton leak (19%) and operate the phosphorylation system (68%) remaining the same across all hepatocytes studied.
Ideal ATP Synthesis
- The study’s findings suggest that the observed decreases in the rates of proton leak and ATP turnover correspond to maintain the effective amount of ATP synthesised per unit of O2 consumed relatively constant with body mass.
- This parity suggests that the observed value, wherein ATP synthesis remains constant despite variations in body mass, may be optimal.
Cite This Article
APA
Porter RK, Brand MD.
(1995).
Causes of differences in respiration rate of hepatocytes from mammals of different body mass.
Am J Physiol, 269(5 Pt 2), R1213-R1224.
https://doi.org/10.1152/ajpregu.1995.269.5.R1213 Publication
Researcher Affiliations
- Department of Biochemistry, University of Cambridge, United Kingdom.
MeSH Terms
- Adenosine Triphosphate / metabolism
- Animals
- Body Weight
- Ferrets
- Horses
- Kinetics
- Liver / cytology
- Liver / metabolism
- Liver / ultrastructure
- Mammals / anatomy & histology
- Mammals / metabolism
- Mice
- Microscopy, Electron
- Mitochondria, Liver / metabolism
- Mitochondria, Liver / ultrastructure
- Oxidation-Reduction
- Oxygen Consumption
- Phosphorylation
- Protons
- Rats
- Sheep
- Swine
Citations
This article has been cited 32 times.- Akingbesote ND, Leitner BP, Jovin DG, Desrouleaux R, Owusu D, Zhu W, Li Z, Pollak MN, Perry RJ. Gene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo. Elife 2023 May 23;12.
- De Vitis C, Capalbo C, Torsello A, Napoli C, Salvati V, Loffredo C, Blandino G, Piaggio G, Auciello FR, Pelliccia F, Salerno G, Simmaco M, Di Magno L, Canettieri G, Coluzzi F, Mancini R, Rocco M, Sciacchitano S. Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients. Antioxidants (Basel) 2022 Oct 8;11(10).
- Harrison JF, Biewener A, Bernhardt JR, Burger JR, Brown JH, Coto ZN, Duell ME, Lynch M, Moffett ER, Norin T, Pettersen AK, Smith FA, Somjee U, Traniello JFA, Williams TM. White Paper: An Integrated Perspective on the Causes of Hypometric Metabolic Scaling in Animals. Integr Comp Biol 2022 Aug 6;62(5):1395-418.
- Pan B, Long H, Yuan Y, Zhang H, Peng Y, Zhou D, Liu C, Xiang B, Huang Y, Zhao Y, Zhao Z, E G. Identification of Body Size Determination Related Candidate Genes in Domestic Pig Using Genome-Wide Selection Signal Analysis. Animals (Basel) 2022 Jul 19;12(14).
- Fang J, Wong HS, Brand MD. Production of superoxide and hydrogen peroxide in the mitochondrial matrix is dominated by site I(Q) of complex I in diverse cell lines. Redox Biol 2020 Oct;37:101722.
- Geisler JG. 2,4 Dinitrophenol as Medicine. Cells 2019 Mar 23;8(3).
- Polymeropoulos ET, Oelkrug R, Jastroch M. Mitochondrial Proton Leak Compensates for Reduced Oxidative Power during Frequent Hypothermic Events in a Protoendothermic Mammal, Echinops telfairi. Front Physiol 2017;8:909.
- Schneider K, Valdez J, Nguyen J, Vawter M, Galke B, Kurtz TW, Chan JY. Increased Energy Expenditure, Ucp1 Expression, and Resistance to Diet-induced Obesity in Mice Lacking Nuclear Factor-Erythroid-2-related Transcription Factor-2 (Nrf2). J Biol Chem 2016 Apr 1;291(14):7754-66.
- Tourmente M, Roldan ER. Mass-Specific Metabolic Rate Influences Sperm Performance through Energy Production in Mammals. PLoS One 2015;10(9):e0138185.
- Rutkai I, Dutta S, Katakam PV, Busija DW. Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries. Am J Physiol Heart Circ Physiol 2015 Nov;309(9):H1490-500.
- Dang CV. A metabolic perspective of Peto's paradox and cancer. Philos Trans R Soc Lond B Biol Sci 2015 Jul 19;370(1673).
- Kitazoe Y, Tanaka M. Evolution of mitochondrial power in vertebrate metazoans. PLoS One 2014;9(6):e98188.
- Morris G, Anderson G, Berk M, Maes M. Coenzyme Q10 depletion in medical and neuropsychiatric disorders: potential repercussions and therapeutic implications. Mol Neurobiol 2013 Dec;48(3):883-903.
- White CR, Kearney MR. Determinants of inter-specific variation in basal metabolic rate. J Comp Physiol B 2013 Jan;183(1):1-26.
- Herculano-Houzel S. The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost. Proc Natl Acad Sci U S A 2012 Jun 26;109 Suppl 1(Suppl 1):10661-8.
- Robbins D, Zhao Y. New aspects of mitochondrial Uncoupling Proteins (UCPs) and their roles in tumorigenesis. Int J Mol Sci 2011;12(8):5285-93.
- Page MM, Stuart JA. Activities of DNA base excision repair enzymes in liver and brain correlate with body mass, but not lifespan. Age (Dordr) 2012 Oct;34(5):1195-209.
- Kitazoe Y, Kishino H, Hasegawa M, Matsui A, Lane N, Tanaka M. Stability of mitochondrial membrane proteins in terrestrial vertebrates predicts aerobic capacity and longevity. Genome Biol Evol 2011;3:1233-44.
- Brand MD, Nicholls DG. Assessing mitochondrial dysfunction in cells. Biochem J 2011 Apr 15;435(2):297-312.
- Williams JB, Miller RA, Harper JM, Wiersma P. Functional linkages for the pace of life, life-history, and environment in birds. Integr Comp Biol 2010 Nov;50(5):855-68.
- Herculano-Houzel S. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution. PLoS One 2011 Mar 1;6(3):e17514.
- Wang F, Fu X, Chen X, Chen X, Zhao Y. Mitochondrial uncoupling inhibits p53 mitochondrial translocation in TPA-challenged skin epidermal JB6 cells. PLoS One 2010 Oct 18;5(10):e13459.
- Singh A, Wirtz M, Parker N, Hogan M, Strahler J, Michailidis G, Schmidt S, Vidal-Puig A, Diano S, Andrews P, Brand MD, Friedman J. Leptin-mediated changes in hepatic mitochondrial metabolism, structure, and protein levels. Proc Natl Acad Sci U S A 2009 Aug 4;106(31):13100-5.
- Hulbert AJ. Membrane fatty acids as pacemakers of animal metabolism. Lipids 2007 Sep;42(9):811-9.
- Orgül S. Blood flow in glaucoma. Br J Ophthalmol 2007 Jan;91(1):3-5.
- Brand MD, Turner N, Ocloo A, Else PL, Hulbert AJ. Proton conductance and fatty acyl composition of liver mitochondria correlates with body mass in birds. Biochem J 2003 Dec 15;376(Pt 3):741-8.
- Roussel D, Harding M, Runswick MJ, Walker JE, Brand MD. Does any yeast mitochondrial carrier have a native uncoupling protein function?. J Bioenerg Biomembr 2002 Jun;34(3):165-76.
- Brand MD. Top-down elasticity analysis and its application to energy metabolism in isolated mitochondria and intact cells. Mol Cell Biochem 1998 Jul;184(1-2):13-20.
- Surwit RS, Wang S, Petro AE, Sanchis D, Raimbault S, Ricquier D, Collins S. Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice. Proc Natl Acad Sci U S A 1998 Mar 31;95(7):4061-5.
- Bond DR, Russell JB. Relationship between intracellular phosphate, proton motive force, and rate of nongrowth energy dissipation (energy spilling) in Streptococcus bovis JB1. Appl Environ Microbiol 1998 Mar;64(3):976-81.
- Thoral E, García-Díaz CC, Persson E, Chamkha I, Elmér E, Ruuskanen S, Nord A. The relationship between mitochondrial respiration, resting metabolic rate and blood cell count in great tits. Biol Open 2024 Mar 1;13(3).
- García-Díaz CC, Chamkha I, Elmér E, Nord A. Plasticity of mitochondrial function safeguards phosphorylating respiration during in vitro simulation of rest-phase hypothermia. FASEB J 2023 Apr;37(4):e22854.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
