Muhammad Adrianes Bachnas, Wiku Andonotopo, Wisnu Prabowo, Eric Edwin Yuliantara, Mochammad Besari Adi Pramono, Julian Dewantiningrum, Efendi Lukas, I Nyoman Hariyasa Sanjaya, Anak Agung Gede Putra Wiradnyana, Anak Agung Ngurah Jaya Kusuma, Ryan Saktika Mulyana, Khanisyah Erza Gumilar, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dovy Djanas, Dudy Aldiansyah, Aloysius Suryawan, Ridwan Abdullah Putra, Anita Deborah Anwar, Cut Meurah Yeni, Nuswil Bernolian, Harry Kurniawan Gondo, Laksmana Adi Krista Nugraha, Waskita Ekamaheswara Kasumba Andanaputra, Wibisana Andika Krista Dharma, Muhammad Alamsyah Aziz, Adhi Pribadi, Sarma Nursani Lumbanraja, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak
Although inflammasome activation has been repeatedly linked to preeclampsia, the field has tended to frame this biology around NLRP3 alone, leaving other sensors - particularly NLRP1 - and their mitochondrial upstream signals only partially examined. Recent experimental work hints at a more intricate narrative in which dysregulated BNIP3-mediated mitophagy and escalating mitochondrial ROS form a convergent pathway toward trophoblast injury. Yet no systematic review has stitched these elements together. Following PRISMA 2020 guidance, we synthesized evidence across experimental, observational, and mechanistic studies, mapping how impaired mitochondrial quality control, oxidative stress, and inflammasome signaling intersect within the placenta and maternal vasculature. The retrieved literature was analyzed for methodological transparency and biological coherence, allowing a layered reconstruction of how BNIP3 overexpression, mitophagy failure, and mtROS collectively prime NLRP1 activation. Across 31 eligible studies, a consistent picture emerged: mitochondrial injury acts less as a by-product and more as a central instigator of the inflammatory cascade that shapes the preeclampsia phenotype. The BNIP3→mtROS→NLRP1 axis appears particularly relevant, even when data are fragmented or derived from heterogeneous models. Recognizing this pathway opens conceptual space for a new therapeutic toolkit - one aimed at mitochondrial stabilization, inflammasome modulation, and restoring trophoblast resilience. © 2026 the author(s), published by De Gruyter, Berlin/Boston.
Fetomaternal Division, Department of Obstetrics and Gynecology, Medical Faculty of Sebelas Maret University, Dr. Moewardi Hospital, Surakarta, Solo, Indonesia; Fetomaternal Division, Women's Health Center, Department of Obstetrics and Gynecology, Eka Hospital Serpong, Tangerang, Banten, Indonesia; Faculty of Medicine, Maranatha Christian University, West Java, Bandung, Indonesia; Fetomaternal Division, Department of Obstetrics and Gynecology, Medical Faculty of Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia; Fetomaternal Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Hasanuddin University of Makassar, Makassar, Indonesia; Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Udayana University, Prof. dr. I.G.N.G Ngoerah General Hospital, Bali, Indonesia; Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Airlangga University, Dr. Soetomo Hospital, Surabaya, Indonesia; Fetomaternal Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Andalas University, M. Djamil General Hospital, West Sumatera, Padang, Indonesia; Fetomaternal Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Sumatera Utara University, H. Adam Malik General Hospital, North Sumatera, Medan, Indonesia; Fetomaternal Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Maranatha Christian University, North Sumatera, Bandung, Indonesia; Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Padjajaran University, Hasan Sadikin General Hospital, West Java, Bandung, Indonesia; Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Syiah Kuala University, Dr. Zainoel Abidin General Hospital, Aceh, Indonesia; Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Sriwijaya University, Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia; Department of Obstetrics and Gynecology, Faculty of Medicine, Wijayakusuma University, East Java, Surabaya, Indonesia; Department of Medicine, Faculty of Medicine, Universitas Diponegoro, Central Java, Semarang, Indonesia; Department of Medicine, Undergraduate Program in Medical Science, Faculty of Medicine, Padjajaran University, West Java, Bandung, Indonesia; Department of Medicine, Undergraduate Program in Medical Science, Faculty of Medicine, Gajah Mada University, Special Region of Yogyakarta, Yogyakarta, Indonesia; Department of Neonatology and Rare Diseases, Medical University of Warsaw, Warsaw, Poland; Department of Obstetrics and Gynecology, Medical School University of Zagreb, Zagreb, Croatia
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