MTX2, encoding Metaxin-2, is an outer mitochondrial membrane protein. It is a subunit of the SAM complex and is involved in maintaining mitochondrial cristae architecture, which is crucial for preventing mtDNA release and subsequent activation of the type I interferon (IFN-I) response via the cGAS-STING pathway [1]. MTX2 also plays a role in various biological processes, and its study in genetic models helps understand its functions.

Knockout of MTX2 in mouse liver induces a robust STING-dependent IFN-I response, highlighting the role of MTX2 in preventing mtDNA-induced inflammation [1]. Conditional podocyte-specific Mtx2 knockout (Pod-Mtx2-KO) mice present podocyte and glomerular abnormalities, microalbuminuria, and mitochondrial dysfunction, indicating MTX2's importance in podocyte function [2]. Loss of MTX2 in patients' primary fibroblasts leads to mitochondrial dysfunction, increased cell senescence, and mitophagy, as well as secondary nuclear morphological defects [3].

In conclusion, MTX2 is essential for maintaining mitochondrial cristae architecture and normal mitochondrial function. Its deficiency leads to mitochondrial dysfunction, inflammation, podocyte injury, and nuclear morphological defects. Studies using KO/CKO mouse models have significantly contributed to understanding its role in aging-related degenerative diseases, mandibuloacral dysplasia, and glomerular diseases [1,2,3].