TIM23TIM17

Tim23Tim17 refers to the core subunits of the translocase of the inner mitochondrial membrane, known as the TIM23 complex. Tim23 and Tim17 are integral inner-membrane proteins that form the central channel through which most presequence-containing precursor proteins are translocated from the outer mitochondrial membrane into the matrix or into the inner membrane. They are essential for mitochondrial protein import and biogenesis.

The TIM23 complex is a multi-subunit machine. In addition to Tim23 and Tim17, the complex includes Tim50, a receptor for presequences in the intermembrane space, and Tim44, which anchors the mitochondrial Hsp70 import motor to the channel from the matrix side. Tim21 can act as a regulatory subunit that influences routing of substrates between complete matrix translocation and lateral insertion into the inner membrane. The motor component of the import system, often referred to as the PAM complex, involves mtHsp70 and its co-chaperones, working with Tim44 to pull cargo into the matrix using ATP hydrolysis. The process is powered by the mitochondrial inner membrane potential (Δψ) and the mtHsp70 motor.

Functionally, precursor proteins are first guided by the TOM complex in the outer membrane and then delivered to the TIM23 translocase. Depending on the substrate and regulatory cues, they are either translocated into the matrix or reorganized into the inner membrane via a lateral gate. This system is central to mitochondrial biogenesis and influences overall cellular energy production.

Evolutionarily, the Tim23Tim17 core is conserved across eukaryotes and is required for viability. Disruption of TIM23 components impairs mitochondrial function and can contribute to disease states linked to mitochondrial protein import defects.