Mff-flox Mouse

Mff, short for mitochondrial fission factor, is a key protein located on the outer mitochondrial membrane. It plays an essential role in mitochondrial fission by recruiting the dynamin-related GTPase Drp1 to mitochondrial fission sites. Mff is also involved in pathways such as the double-stranded RNA-induced antiviral response via mitochondrial antiviral signaling (MAVS), and is regulated by processes like AMP-activated protein kinase (AMPK)-mediated phosphorylation and alternative pre-mRNA splicing [5]. Its proper function is crucial for maintaining mitochondrial homeostasis, which is vital for overall cell health and function. Genetic models, such as gene knockout (KO) mouse models, have been instrumental in studying Mff's functions.

In obesity, the deletion of CerS6, which synthesizes C16:0 sphingolipids that interact with Mff, protects from obesity and insulin resistance, suggesting Mff's role in obesity-induced mitochondrial fragmentation [1]. In cardiac ischemia/reperfusion injury, DUSP1 transgenic mice, with reduced Mff-required mitochondrial fission, show smaller infarcted areas and improved myocardial function compared to wild-type mice, highlighting Mff's role in this injury [2]. In renal fibrosis, knockdown of DKK3, which upregulates MFF, alleviates kidney damage and fibrosis, indicating Mff's contribution to this disease [3]. In acute kidney injury, RCAN1 deficiency, which reduces Mff-mediated mitochondrial fission, protects against kidney damage and cell apoptosis [4]. In ovarian cancer, inhibition of MFF, which is highly expressed and promoted by CPT1A through succinylation, significantly inhibits cancer progression in vivo [6].

In conclusion, Mff is essential for mitochondrial fission and is involved in multiple disease-related processes. The use of KO/CKO mouse models has been crucial in revealing Mff's role in diseases such as obesity, cardiac ischemia/reperfusion injury, renal fibrosis, acute kidney injury, and ovarian cancer. Understanding Mff's functions provides potential therapeutic targets for these diseases.