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Volume 26
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10.3390/ijms26167759
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Assessing the Function of Porcine A Kinase-Interacting Protein 1 (AKIP1) In Vitro—A Central Regulator of Oxidative Stress and Mitochondrial Functions

by
Agnieszka Bak
1,†,
Arne Hinrichs
2,†,
Anna Schwaiger
3,
Tobias Fromme
3,
Andrea Fischer
1,
Mayuko Kurome
2,
Valeri Zakhartchenko
2,
Barbara Kessler
2,
Martin Klingenspor
3,
Eckhard Wolf
2,
Angelika Schnieke
1 and
Konrad Fischer
1,*
1
Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, 85354 Freising, Germany
2
Chair of Molecular Animal Breeding and Biotechnology, Ludwig-Maximillians-Universität München, 85764 Oberschleissheim, Germany
3
Chair of Molecular Nutritional Medicine, School of Life Sciences Weihenstephan, Technische Universität München, 85354 Freising, Germany
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(16), 7759; https://doi.org/10.3390/ijms26167759
Submission received: 6 July 2025 / Revised: 4 August 2025 / Accepted: 11 August 2025 / Published: 11 August 2025
(This article belongs to the Special Issue Novel Genotypes and Experimental Advances in Xenotransplantation)
Versions Notes

Abstract

Oxidative stress plays a central role in numerous conditions, including cancer, cardiovascular and neurodegenerative diseases, diabetes, chronic inflammation, and organ transplantation. In transplantation, oxidative stress leads to mitochondrial dysfunction, DNA and protein damage, lipid peroxidation, and activation of pro-inflammatory pathways such as NF-κB, ultimately impairing cell viability and organ function. A Kinase-Interacting Protein 1 (AKIP1) has been linked to oxidative stress regulation in transgenic mouse models. To investigate this further in a livestock setting, we generated AKIP1 transgenic pigs and assessed AKIP1’s protective role against oxidative-stress-induced cell death, including apoptosis, necrosis, and ferroptosis in vitro. Our cellular analyses revealed reduced apoptosis (caspase-3/7 activity), suppressed MPTP-mediated necrosis, and decreased lipid peroxidation, suggesting protection from ferroptosis. Additionally, we observed lower mitochondrial superoxide production and enhanced mitochondrial respiration and recovery following H2O2-induced oxidative challenge. This is the first study to examine AKIP1 in porcine cells, providing a unique and translational platform for studying oxidative injury in a physiologically relevant species. Our in vitro data reveal that AKIP1 overexpression enhances antioxidant defenses and mitochondrial stability, offering future potential for improving graft survival in xenotransplantation.
Keywords: A Kinase-Interacting Protein 1; AKIP1; oxidative stress; mitochondria; ROS production; pig; organ transplantation; ischemia–reperfusion injury A Kinase-Interacting Protein 1; AKIP1; oxidative stress; mitochondria; ROS production; pig; organ transplantation; ischemia–reperfusion injury

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MDPI and ACS Style

Bak, A.; Hinrichs, A.; Schwaiger, A.; Fromme, T.; Fischer, A.; Kurome, M.; Zakhartchenko, V.; Kessler, B.; Klingenspor, M.; Wolf, E.; et al. Assessing the Function of Porcine A Kinase-Interacting Protein 1 (AKIP1) In Vitro—A Central Regulator of Oxidative Stress and Mitochondrial Functions. Int. J. Mol. Sci. 2025, 26, 7759. https://doi.org/10.3390/ijms26167759

AMA Style

Bak A, Hinrichs A, Schwaiger A, Fromme T, Fischer A, Kurome M, Zakhartchenko V, Kessler B, Klingenspor M, Wolf E, et al. Assessing the Function of Porcine A Kinase-Interacting Protein 1 (AKIP1) In Vitro—A Central Regulator of Oxidative Stress and Mitochondrial Functions. International Journal of Molecular Sciences. 2025; 26(16):7759. https://doi.org/10.3390/ijms26167759

Chicago/Turabian Style

Bak, Agnieszka, Arne Hinrichs, Anna Schwaiger, Tobias Fromme, Andrea Fischer, Mayuko Kurome, Valeri Zakhartchenko, Barbara Kessler, Martin Klingenspor, Eckhard Wolf, and et al. 2025. "Assessing the Function of Porcine A Kinase-Interacting Protein 1 (AKIP1) In Vitro—A Central Regulator of Oxidative Stress and Mitochondrial Functions" International Journal of Molecular Sciences 26, no. 16: 7759. https://doi.org/10.3390/ijms26167759

APA Style

Bak, A., Hinrichs, A., Schwaiger, A., Fromme, T., Fischer, A., Kurome, M., Zakhartchenko, V., Kessler, B., Klingenspor, M., Wolf, E., Schnieke, A., & Fischer, K. (2025). Assessing the Function of Porcine A Kinase-Interacting Protein 1 (AKIP1) In Vitro—A Central Regulator of Oxidative Stress and Mitochondrial Functions. International Journal of Molecular Sciences, 26(16), 7759. https://doi.org/10.3390/ijms26167759

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