Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 30:13:920034.
doi: 10.3389/fphys.2022.920034. eCollection 2022.

Effects of Lactate Administration on Mitochondrial Respiratory Function in Mouse Skeletal Muscle

Kenya Takahashi  1 , Yuki Tamura  2   3 , Yu Kitaoka  4 , Yutaka Matsunaga  1 , Hideo Hatta  1
Affiliations

Effects of Lactate Administration on Mitochondrial Respiratory Function in Mouse Skeletal Muscle

Kenya Takahashi et al. Front Physiol. .

Abstract

Recent evidence has shown that mitochondrial respiratory function contributes to exercise performance and metabolic health. Given that lactate is considered a potential signaling molecule that induces mitochondrial adaptations, we tested the hypothesis that lactate would change mitochondrial respiratory function in skeletal muscle. Male ICR mice (8 weeks old) received intraperitoneal injection of PBS or sodium lactate (1 g/kg BW) 5 days a week for 4 weeks. Mitochondria were isolated from freshly excised gastrocnemius muscle using differential centrifugation and were used for all analyses. Lactate administration significantly enhanced pyruvate + malate- and glutamate + malate-induced (complex I-driven) state 3 (maximal/ATP synthesis-coupled) respiration, but not state 2 (basal/proton conductance) respiration. In contrast, lactate administration significantly decreased succinate + rotenone-induced (complex II-driven) state 3 and 2 respiration. No significant differences were observed in malate + octanoyl-l-carnitine-induced state 3 or 2 respiration. The enzymatic activity of complex I was tended to increase and those of complexes I + III and IV were significantly increased after lactate administration. No differences were observed in the activities of complexes II or II + III. Moreover, lactate administration increased the protein content of NDUFS4, a subunit of complex I, but not those of the other components. The present findings suggest that lactate alters mitochondrial respiratory function in skeletal muscle.

Keywords: lactate; mitochondria; oxygen consumption rate; skeletal muscle; supercomplex.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Oxygen consumption rate (OCR) in isolated mitochondria. (A) Pyruvate + malate-induced (complex I-driven) OCR. (B) Glutamate + malate-induced (complex I-driven) OCR. (C) Succinate + rotenone-induced (complex II-driven) OCR. (D) Malate + octanoyl-l-carnitine-induced OCR. Data are expressed as mean ± SD and are normalized to citrate synthase (CS) activity. Control group: n = 10, Lactate group: n = 9. Unpaired Student’s t-test was used for statistical evaluation.
FIGURE 2
FIGURE 2
Mitochondrial respiratory chain enzyme activity. Data are expressed as mean ± SD and are normalized to citrate synthase (CS) activity. Control group: n = 10, Lactate group: n = 9. Unpaired Student’s t-test was used for statistical evaluation.
FIGURE 3
FIGURE 3
Correlation between state 3 oxygen consumption rate (OCR) and respiratory chain enzyme activity. (A) pyruvate + malate-induced (complex I-driven) state 3 OCR against complex I enzyme activity. (B) glutamate + malate-induced (complex I-driven) state 3 OCR against complex I enzyme activity. (C) succinate + rotenone-induced (complex II-driven) state 3 OCR against complex II enzyme activity. Data are expressed as mean ± SD. Control group: n = 10, Lactate group: n = 9. The correlation was studied using least-squares linear regressions, followed by the Pearson’s correlation coefficient test.
FIGURE 4
FIGURE 4
The protein content of respiratory chain components (A) and supercomplex assembly (B) in isolated mitochondria. Data are expressed as mean ± SD and are normalized to citrate synthase (CS) protein. Control group: n = 10, Lactate group: n = 9. Unpaired Student’s t-test was used for statistical evaluation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ahmed K., Tunaru S., Tang C., Müller M., Gille A., Sassmann A., et al. (2010). An Autocrine Lactate Loop Mediates Insulin-dependent Inhibition of Lipolysis through GPR81. Cell. Metab. 11, 311–319. 10.1016/j.cmet.2010.02.012 - DOI - PubMed
    1. Alam M. T., Manjeri G. R., Rodenburg R. J., Smeitink J. A. M., Notebaart R. A., Huynen M., et al. (2015). Skeletal Muscle Mitochondria of NDUFS4−/− Mice Display Normal Maximal Pyruvate Oxidation and ATP Production. Biochimica Biophysica Acta (BBA) - Bioenergetics 1847, 526–533. 10.1016/j.bbabio.2015.02.006 - DOI - PubMed
    1. Assouline Z., Jambou M., Rio M., Bole-Feysot C., de Lonlay P., Barnerias C., et al. (2012). A Constant and Similar Assembly Defect of Mitochondrial Respiratory Chain Complex I Allows Rapid Identification of NDUFS4 Mutations in Patients with Leigh Syndrome. Biochimica Biophysica Acta (BBA) - Mol. Basis Dis. 1822, 1062–1069. 10.1016/j.bbadis.2012.01.013 - DOI - PubMed
    1. Bishop D. J., Botella J., Genders A. J., Lee M. J.-C., Saner N. J., Kuang J., et al. (2019). High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions. Physiology 34, 56–70. 10.1152/physiol.00038.2018 - DOI - PubMed
    1. Bishop D. J., Granata C., Eynon N. (2014). Can We Optimise the Exercise Training Prescription to Maximise Improvements in Mitochondria Function and Content? Biochimica Biophysica Acta (BBA) - General Subj. 1840, 1266–1275. 10.1016/j.bbagen.2013.10.012 - DOI - PubMed

LinkOut - more resources