Aifm3, apoptosis-inducing factor, mitochondrion-associated 3, is a mitochondrial protein. It has been implicated in various biological functions.

In kidney development, it is considered important for promoting cell survival, energy production in nephrogenesis, and tubular maturation [1]. It may also be involved in the regulation of cell death-related processes. GSDMD, a key regulator in pyroptosis, is reported to regulate the AMPK/PGC-1α pathway to target Aifm3, organizing the mitochondrial electron transport chain and promoting a switch from oxidative phosphorylation to glycolysis during embryonic cortical development [2].

In disease-related studies, Aifm3 shows potential as a biomarker and therapeutic target.

In cholangiocarcinoma (CCA), it is over-expressed, and its serum levels can be a prognostic biomarker. Bioinformatic analysis predicts that AIFM3 interacts with FMNL3 and is involved in tumor cell motilities, and its gene silencing significantly decreases CCA cell migration/invasion [3].

In breast cancer, AIFM3 is more expressed in cancer tissues, and its expression is associated with tumor size, lymph node metastasis, TNM stage, and molecular typing, being related to shorter overall and disease-free survival [4].

In medullary thyroid carcinoma, there are recurrent copy number gains of AIFM3, and its CNA status correlates with AJCC staging [5].

In CCA, it could be a potential target molecule for chemotherapy as it is aberrantly expressed only in the mitochondria of CCA tissues [6].

In conclusion, Aifm3 plays important roles in kidney development and energy-related metabolic processes during embryonic development. In cancer, it shows potential as a biomarker for prognosis and as a therapeutic target in diseases like cholangiocarcinoma, breast cancer, and medullary thyroid carcinoma. The study of Aifm3 using genetic models helps in understanding its functions in normal and disease-related biological processes.

References:

1. Lozic, Mirela, Minarik, Luka, Racetin, Anita, Saraga Babic, Mirna, Vukojevic, Katarina. 2021. CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development. In International journal of molecular sciences, 22, . doi:10.3390/ijms22179183. https://pubmed.ncbi.nlm.nih.gov/34502088/

2. Ma, Hongyan, Jia, Huiyang, Zou, Wenzheng, Yuan, Chenqi, Jiao, Jianwei. 2024. Gasdermin D Mediated Mitochondrial Metabolism Orchestrate Neurogenesis Through LDHA During Embryonic Development. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2402285. doi:10.1002/advs.202402285. https://pubmed.ncbi.nlm.nih.gov/39033542/

3. Chua-On, Daraporn, Proungvitaya, Tanakorn, Techasen, Anchalee, Araki, Norie, Proungvitaya, Siriporn. . Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells. In Cancer genomics & proteomics, 19, 35-49. doi:10.21873/cgp.20302. https://pubmed.ncbi.nlm.nih.gov/34949658/

4. Zheng, Ang, Zhang, Lin, Song, Xinyue, Wei, Minjie, Jin, Feng. 2019. Clinical implications of a novel prognostic factor AIFM3 in breast cancer patients. In BMC cancer, 19, 451. doi:10.1186/s12885-019-5659-4. https://pubmed.ncbi.nlm.nih.gov/31088422/

5. Araujo, Aline Neves, Camacho, Cléber Pinto, Mendes, Thais Biude, Maciel, Rui Monteiro de Barros, Cerutti, Janete Maria. 2021. Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma. In Cancers, 13, . doi:10.3390/cancers13020218. https://pubmed.ncbi.nlm.nih.gov/33435319/

6. Chua-On, Daraporn, Proungvitaya, Tanakorn, Techasen, Anchalee, Sungkhamanon, Sakkarn, Proungvitaya, Siriporn. 2016. High expression of apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) in human cholangiocarcinoma. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 13659-13667. doi:. https://pubmed.ncbi.nlm.nih.gov/27473083/