TIM23Tim21

TIM23Tim21 refers to the TIM23 translocase complex of the inner mitochondrial membrane that includes the Tim21 subunit. The TIM23 complex mediates import of most nuclear-encoded mitochondrial proteins bearing N-terminal presequences into the matrix and, for some substrates, their insertion into the inner membrane. Tim21 is a regulatory subunit that associates with the TIM23 complex and modulates its activity to influence the routing of substrates between matrix import and inner membrane insertion.

Composition and function: The core TIM23 complex includes Tim23 and Tim17, forming the translocation channel, with Tim50 contributing receptor functions. Tim21 binds to Tim23 and Tim17 and helps tune the decision between matrix targeting and lateral insertion into the inner membrane. This Tim21-containing form of TIM23 can act in concert with other import components to accommodate substrates under different growth or stress conditions.

Structure and localization: Tim21 is a small inner-membrane protein with a single transmembrane segment; its connecting regions contact both sides of the membrane to interact with TIM23 components. The exact topology can vary between organisms, but Tim21 is consistently associated with the TIM23 translocase.

Genetics and evolution: In baker's yeast (Saccharomyces cerevisiae), TIM21 is encoded by TIM21. Homologs are found in diverse fungi and other eukaryotes, highlighting a conserved regulatory module within the mitochondrial import machinery.

Research and significance: Studies of TIM23Tim21 shed light on how cells regulate mitochondrial biogenesis and proteostasis. Genetic or biochemical perturbation of Tim21 can impair import efficiency for certain substrates and affect growth under stress, illustrating the importance of translocase regulation in mitochondrial function.