ARK5 enhances cell survival associated with mitochondrial morphological dynamics from fusion to fission in human multiple myeloma cells

• DOI: 10.1038/s41420-024-01814-w
• Publication Date: 2024-01-29T04:42:10Z
• Authors: Sivasundaram Karnan; Ichiro Hanamura; Akinobu Ota; Lam Quang Vu; Kaori Uchino; Tomohiro Horio; Satsuki Murakami; Shohei Mizuno; Md Lutfur Rahman; Md Wahiduzzaman; Muhammad Nazmul H...; Mrityunjoy Biswas; Toshinori Hyodo; Hideaki Ito; Atsushi Suzuki; Hiroyuki Konishi; Shinobu Tsuzuki; Yoshitaka Hosokawa; Akiyoshi Takami
• Keywords: MFN2; MFN1

Abstract 5′ adenosine monophosphate–activated protein kinase–related kinase 5 (ARK5) is involved in mitochondrial ATP production and associated with poor prognosis of multiple myeloma (MM). However, the molecular mechanisms ARK5 MM remain largely unknown. This study examined pathogenic role mitochondria by using genetically modified isogenic cell clones or without human lines, KMS-11 Sachi, which overexpress . The biallelic knockout (ARK5-KO) inhibited proliferation, colony formation, migration increased apoptosis. Mitochondrial fusion was enhanced ARK5-KO cells, unlike wild-type (ARK5-WT) exhibited fission. Furthermore, cells demonstrated a lower phosphorylated dynamin–related 1 at serine 616, higher expression mitofusin-1 (MFN1) MFN2, optic atrophy level ATP, levels lactate reactive oxygen species than ARK5-WT cells. Our findings suggest that ARK5-enhanced can survive fission activity. first revealed relationship between morphological dynamics. Thus, our outcomes show novel aspects biology ARK5, afford more advanced treatment approach for unfavorable expressing ARK5.