Features of the circadian rhythm in the size of the mitochondria of rat hepatocytes under conditions of dark deprivation and chronic alcohol intoxication
- Authors: Areshidze D.A.1
-
Affiliations:
- Petrovsky National Research Centre of Surgery
- Issue: Vol 161, No 4 (2023)
- Pages: 5-14
- Section: Original Study Articles
- Submitted: 08.04.2024
- Accepted: 16.05.2024
- Published: 15.10.2023
- URL: https://j-morphology.com/1026-3543/article/view/630117
- DOI: https://doi.org/10.17816/morph.630117
- ID: 630117
Cite item
Abstract
BACKGROUND: Circadian rhythms of body functions and processes are normally strictly coordinated with each other and environmental factors, which ensures optimal maintenance of the functioning of body organs and systems. However, no studies have assessed the circadian rhythms of hepatocyte organelles under experimental conditions.
AIM: To assess the daily dynamics of the cross-sectional area of rat hepatocyte mitochondria under conditions of dark deprivation, chronic alcohol intoxication, and their combination.
MATERIALS AND METHODS: The study analyzed 80 male and 80 female Wistar rats, divided into 4 groups of each sex: group 1 was kept under a fixed light regimen, group 2 under dark deprivation, group 3 in the same conditions as the control group but were subjected to chronic alcohol intoxication, and group 4 under dark deprivation and chronic alcohol intoxication. Liver samples, after fixation and wiring, were analyzed under a transmission electron microscope. Micromorphometric methods were used to assess the mitochondrial apparatus of hepatocytes.
RESULTS: In rat hepatocytes from the experimental groups of both sexes, the circadian rhythm of the cross-sectional area of the mitochondria with similar parameters was detected. Dark deprivation and chronic alcohol intoxication, acting both separately and together, resulted in the restructuring of mitochondrial size distribution, which was more pronounced in males.
CONCLUSION: The study indicates that the circadian rhythm of mitochondrial size is dependent on the lighting regimen and toxic effects of ethanol and its metabolites. The size ranges of the mitochondria in the hepatocytes of females, compared with those of males, are more resistant to the effects of dark deprivation and alcohol intoxication.
Keywords
Full Text

About the authors
David A. Areshidze
Petrovsky National Research Centre of Surgery
Author for correspondence.
Email: labcelpat@mail.ru
ORCID iD: 0000-0003-3006-6281
SPIN-code: 4348-6781
Cand. Sci. (Biology)
Russian Federation, MoscowReferences
- Chibisov SM, Rappoport SI, Blagonravov ML. Chronobiology and chronomedicine. Moscow: Izd-vo RUDN; 2018. 828 p. (In Russ).
- Forger DB. Biological clocks, rhythms, and oscillations: the theory of biological timekeeping. Cambridge (MA): MIT Press; 2017.
- McKenna H, van der Horst GTJ, Reiss I, Martin D. Clinical chronobiology: a timely consideration in critical care medicine. Crit Care. 2018;22(1):124. doi: 10.1186/s13054-018-2041-x
- Walker WH 2nd, Bumgarner JR, Walton JC, et al. Light pollution and cancer. Int J Mol Sci. 2020;21(24):9360. doi: 10.3390/ijms21249360
- Chaix A, Lin T, Le HD, et al. Time-restricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock. Cell Metab. 2019;29(2):303–319.e4. doi: 10.1016/j.cmet.2018.08.004
- Panda S, Poirier GG, Kay SA. tej defines a role for poly(ADP-ribosyl)ation in establishing period length of the arabidopsis circadian oscillator. Dev Cell. 2002;3(1):51–61. doi: 10.1016/s1534-5807(02)00200-9
- Roenneberg T, Merrow M. The circadian clock and human health. Curr Biol. 2016;26(10): R432-R443. doi: 10.1016/j.cub.2016.04.011
- Zimmet P, Alberti KGMM, Stern N, et al. The circadian syndrome: is the metabolic syndrome and much more! J Intern Med. 2019;286(2):181–191. doi: 10.1111/joim.12924
- Nicolaides NC, Chrousos GP. Sex differences in circadian endocrine rhythms: clinical implications. Eur J Neurosci. 2020;52(1):2575–2585. doi: 10.1111/ejn.14692
- Walton JC, Bumgarner JR, Nelson RJ. Sex differences in circadian rhythms. Cold Spring Harb Perspect Biol. 2022;14(7):a039107. doi: 10.1101/cshperspect.a039107
- Kim P, Oster H, Lehnert H, et al. Coupling the circadian clock to homeostasis: the role of period in timing physiology. Endocr Rev. 2019;40(1):66–95. doi: 10.1210/er.2018-00049
- Shi D, Chen J, Wang J, et al. Circadian clock genes in the metabolism of non-alcoholic fatty liver disease. Front Physiol. 2019;10:423. doi: 10.3389/fphys.2019.00423
- de Assis LVM, Demir M, Oster H. The role of the circadian clock in the development, progression, and treatment of non-alcoholic fatty liver disease. Acta Physiol (Oxf). 2023;237(3):e13915. doi: 10.1111/apha.13915
- Michel S, Meijer JH. From clock to functional pacemaker. Eur J Neurosci. 2020;51(1):482–493. doi: 10.1111/ejn.14388
- Li H, Zhang S, Zhang W, et al. Endogenous circadian time genes expressions in the liver of mice under constant darkness. BMC Genomics. 2020;21(1):224. doi: 10.1186/s12864-020-6639-4
- Areshidze DA, Kozlova MA, Makartseva LA, et al. Influence of constant lightning on liver health: an experimental study. Environ Sci Pollut Res Int. 2022;29(55):83686–83697. doi: 10.1007/s11356-022-21655-3
- Sato K, Meng F, Francis H, et al. Melatonin and circadian rhythms in liver diseases: functional roles and potential therapies. J Pineal Res. 2020;68(3):e12639. doi: 10.1111/jpi.12639
- Stevens RG, Davis S, Mirick DK, et al. Alcohol consumption and urinary concentration of 6-sulfatoxymelatonin in healthy women. Epidemiology. 2000;11(6):660–665. doi: 10.1097/00001648-200011000-00008
- Audebrand A, Désaubry L, Nebigil CG. Targeting GPCRs against cardiotoxicity induced by anticancer treatments. Front Cardiovasc Med. 2020;6:194. doi: 10.3389/fcvm.2019.00194
- Talib WH, Alsayed AR, Abuawad A, et al. Melatonin in cancer treatment: current knowledge and future opportunities. Molecules. 2021;26(9):2506. doi: 10.3390/molecules26092506
- Voigt RM, Forsyth CB, Keshavarzian A. Circadian rhythms: a regulator of gastrointestinal health and dysfunction. Expert Rev Gastroenterol Hepatol. 2019;13(5):411–424. doi: 10.1080/17474124.2019.1595588
- Huang MC, Ho CW, Chen CH, et al. Reduced expression of circadian clock genes in male alcoholic patients. Alcohol Clin Exp Res. 2010;34(11):1899–1904. doi: 10.1111/j.1530-0277.2010.01278.x
- Aviram R, Adamovich Y, Asher G. Circadian organelles: rhythms at all scales. Cells. 2021;10(9):2447. doi: 10.3390/cells10092447
- Wang J, Mauvoisin D, Martin E, et al. Nuclear proteomics uncovers diurnal regulatory landscapes in mouse liver. Cell Metab. 2017;25(1):102–117. doi: 10.1016/j.cmet.2016.10.003
- Yeung J, Naef F. Rhythms of the genome: circadian dynamics from chromatin topology, tissue-specific gene expression, to behavior. Trends Genet. 2018;34(12):915–926. doi: 10.1016/j.tig.2018.09.005
- Wai T, Langer T. Mitochondrial dynamics and metabolic regulation. Trends Endocrinol Metab. 2016;27(2):105–117. doi: 10.1016/j.tem.2015.12.001
- Braakman I, Bulleid NJ. Protein folding and modification in the mammalian endoplasmic reticulum. Annu Rev Biochem. 2011;80:71–99. doi: 10.1146/annurev-biochem-062209-093836
- Chedid A, Nair V. Diurnal rhythm in endoplasmic reticulum of rat liver: electron microscopic study. Science. 1972;175(4018):176–179. doi: 10.1126/science.175.4018.176
- Ma D, Panda S, Lin JD. Temporal orchestration of circadian autophagy rhythm by C/EBPβ. EMBO J. 2011;30(22):4642–4651. doi: 10.1038/emboj.2011.322
- Kozlova MA, Kirillov YA, Makartseva LA, et al. Morphofunctional state and circadian rhythms of the liver under the influence of chronic alcohol intoxication and constant lighting. Int J Mol Sci. 2021;22(23):13007. doi: 10.3390/ijms222313007
- Areshidze DA, Kozlova MA. Morphofunctional state and circadian rhythms of the liver of female rats under the influence of chronic alcohol intoxication and constant lighting. Int J Mol Sci. 2022;23(18):10744. doi: 10.3390/ijms231810744
- Stepanov AV, Baidyuk EV, Sakuta GA. The features of mitochondria of cardiomyocytes from rats with chronic heart failure. Cell and Tissue Biology. 2017;11(6):458–465. EDN: XXNPXV doi: 10.1134/S1990519X17060086
- Tsang AH, Astiz M, Leinweber B, Oster H. Rodent models for the analysis of tissue clock function in metabolic rhythms research. Front Endocrinol (Lausanne). 2017;8:27. doi: 10.3389/fendo.2017.00027
- Balkanov AS, Rozanov ID, Golanov AV, et al. Endothelium changes of peritumoral zone capillaries after brain glioblastoma adjuvant radiation therapy. Clinical and Experimental Morphology. 2021;10(1):33–40. EDN: KOULJY doi: 10.31088/CEM2021.10.1.33-40
- Kurbat MN, Kravchuk RI, Ostrovskaya OB. Effect of melatonin on the morphology of mitochondria and other cellular components of the hepatocyte. Hepatology and Gastroenterology. 2018;2(2):138–142. EDN: TTCMUQ
- Otsuka K, Watanabe H. Experimental and clinical chronocardiology. Chronobiologia. 1990;17(2):135–163.
- Cornelissen G. Cosinor-based rhythmometry. Theor Biol Med Model. 2014;11:16. doi: 10.1186/1742-4682-11-16
- Jacobi D, Liu S, Burkewitz K, et al. Hepatic bmal1 regulates rhythmic mitochondrial dynamics and promotes metabolic fitness. Cell Metab. 2015;22(4):709–720. doi: 10.1016/j.cmet.2015.08.006
- Oliva-Ramírez J, Moreno-Altamirano MM, Pineda-Olvera B, et al. Crosstalk between circadian rhythmicity, mitochondrial dynamics and macrophage bactericidal activity. Immunology. 2014;143(3):490–497. doi: 10.1111/imm.12329
- Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem. 2010;47:69–84. doi: 10.1042/bse0470069
- de Goede P, Wefers J, Brombacher EC, et al. Circadian rhythms in mitochondrial respiration. J Mol Endocrinol. 2018;60(3):R115–R130. doi: 10.1530/JME-17-0196
- Manella G, Asher G. The circadian nature of mitochondrial biology. Front Endocrinol (Lausanne). 2016;7:162. doi: 10.3389/fendo.2016.00162
- Darshi M, Mendiola VL, Mackey MR, et al. ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function. J Biol Chem. 2011;286(4):2918–2932. doi: 10.1074/jbc.M110.171975
- Vue Z, Garza-Lopez E, Neikirk K, et al. 3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex. Aging Cell. 2023;22(12):e14009. doi: 10.1111/acel.14009
- Mizuno M, Kuno A, Yano T, et al. Empagliflozin normalizes the size and number of mitochondria and prevents reduction in mitochondrial size after myocardial infarction in diabetic hearts. Physiol Rep. 2018;6(12):e13741. doi: 10.14814/phy2.13741
- Mazure NM, Brahimi-Horn MC, Pouysségur J. Hypoxic mitochondria: accomplices in resistance. Bull Cancer. 2011;98(5):40–46. doi: 10.1684/bdc.2011.1360
- Zhuang Y, Jiang W, Zhao Z, et al. Ion channel-mediated mitochondrial volume regulation and its relationship with mitochondrial dynamics. Channels (Austin). 2024;18(1):2335467. doi: 10.1080/19336950.2024.2335467
Supplementary files
