TIMM23

TIMM23, short for translocase of the inner mitochondrial membrane 23, is a core component of the mitochondrial TIM23 translocase. This multi-protein complex resides in the inner mitochondrial membrane and mediates the import of most nuclear-encoded preproteins that are destined for the mitochondrial matrix or inner membrane. The TIM23 complex accepts precursor polypeptides from the TOM translocase in the outer membrane and works in concert with Tim50, which serves as a presequence receptor on the intermembrane space side, to guide translocation through the inner membrane.

Tim23 forms a channel in combination with Tim17, together constituting a heterooligomeric pore through which polypeptides pass. Depending on the targeting information, substrates are either fully translocated into the matrix or laterally inserted into the inner membrane via stop-transfer mechanisms. The import motor, primarily the mtHsp70 system together with Tim44, engages with TIM23 to power translocation into the matrix.

Tim23 is a conserved inner membrane protein found across eukaryotes, with the human TIMM23 gene encoding the Tim23 protein. The protein is essential for cellular viability, and disruption of TIM23 function impairs mitochondrial protein import and organelle performance. While direct human disease associations are limited, defects in mitochondrial protein import pathways—including TIM23-related steps—are linked to mitochondrial dysfunction and related disease phenotypes in experimental systems and clinical observations.