Role of Tim17 in coupling the import motor to the translocation channel of the mitochondrial presequence translocase

Demishtein-Zohary, Keren; Günsel, Umut; Marom, Milit; Banerjee, Rupa; Neupert, Walter; Azem, Abdussalam; Mokranjac, Dejana

doi:10.7554/elife.22696

Cited by 36 publications

(25 citation statements)

References 44 publications

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“…The mitochondria of Tim17 G20D cells also show slightly decreased levels of Tim17 and Tim23 overall (Supplementary Fig. 2c,d), which is in agreement with recently published data reporting that mutations in the transmembrane segment TM1 (residues 18 to 35) of Tim17 lead to destabilized interactions with Tim 23 (ref. 13).…”

Section: Resultssupporting

confidence: 92%

Stendomycin selectively inhibits TIM23-dependent mitochondrial protein import

et al. 2017

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Tim17 and Tim23 are the main subunits of the TIM23 complex, one of the two major essential mitochondrial inner-membrane protein translocon machineries (TIMs). No chemical probes that specifically inhibit TIM23-dependent protein import were known to exist. Here we show that the natural product stendomycin, produced by Streptomyces hygroscopicus, is a potent and specific inhibitor of the TIM23 complex in yeast and mammalian cells. Furthermore, stendomycin-mediated blockage of the TIM23 complex does not alter normal processing of the major regulatory mitophagy kinase PINK1, but TIM23 is required to stabilize PINK1 on the outside of mitochondria to initiate mitophagy upon membrane depolarization.

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Section: Resultssupporting

confidence: 92%

Stendomycin selectively inhibits TIM23-dependent mitochondrial protein import

et al. 2017

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“…2017 ). Interestingly, GiTim17 contains the conserved arginine residue responsible for Tim44 binding in yeast mitochondria ( Demishtein-Zohary et al. 2017 ) ( fig.…”

Section: Resultsmentioning

confidence: 99%

A Single Tim Translocase in the Mitosomes of Giardia intestinalis Illustrates Convergence of Protein Import Machines in Anaerobic Eukaryotes

Pyrihová

Motyčková

Voleman

et al. 2018

Genome Biology and Evolution

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Mitochondria have evolved diverse forms across eukaryotic diversity in adaptation to anoxia. Mitosomes are the simplest and the least well-studied type of anaerobic mitochondria. Transport of proteins via TIM complexes, composed of three proteins of the Tim17 protein family (Tim17/22/23), is one of the key unifying aspects of mitochondria and mitochondria-derived organelles. However, multiple experimental and bioinformatic attempts have so far failed to identify the nature of TIM in mitosomes of the anaerobic metamonad protist, Giardia intestinalis, one of the few experimental models for mitosome biology. Here, we present the identification of a single G. intestinalis Tim17 protein (GiTim17), made possible only by the implementation of a metamonad-specific hidden Markov model. While very divergent in primary sequence and in predicted membrane topology, experimental data suggest that GiTim17 is an inner membrane mitosomal protein, forming a disulphide-linked dimer. We suggest that the peculiar GiTim17 sequence reflects adaptation to the unusual, detergent resistant, inner mitosomal membrane. Specific pull-down experiments indicate interaction of GiTim17 with mitosomal Tim44, the tethering component of the import motor complex. Analysis of TIM complexes across eukaryote diversity suggests that a “single Tim” translocase is a convergent adaptation of mitosomes in anaerobic protists, with Tim22 and Tim17 (but not Tim23), providing the protein backbone.

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“…6 ). The large matrix-exposed loop of Tim17 (loop 1) interacts with one CTD patch and the small loop (loop 3) of Tim17 with the other [ 66 , 74 ]. Loop 1 of Tim17 crosslinks to Pam17, the nonessential PAM component [ 75 ].…”

Section: Hsp70 On the Matrix/lumenal Side Of The Membranementioning

confidence: 99%

Hsp70 at the membrane: driving protein translocation

2018

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Efficient movement of proteins across membranes is required for cell health. The translocation process is particularly challenging when the channel in the membrane through which proteins must pass is narrow—such as those in the membranes of the endoplasmic reticulum and mitochondria. Hsp70 molecular chaperones play roles on both sides of these membranes, ensuring efficient translocation of proteins synthesized on cytosolic ribosomes into the interior of these organelles. The “import motor” in the mitochondrial matrix, which is essential for driving the movement of proteins across the mitochondrial inner membrane, is arguably the most complex Hsp70-based system in the cell.

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Role of Tim17 in coupling the import motor to the translocation channel of the mitochondrial presequence translocase

Cited by 36 publications

References 44 publications

Stendomycin selectively inhibits TIM23-dependent mitochondrial protein import

Stendomycin selectively inhibits TIM23-dependent mitochondrial protein import

A Single Tim Translocase in the Mitosomes of Giardia intestinalis Illustrates Convergence of Protein Import Machines in Anaerobic Eukaryotes

Hsp70 at the membrane: driving protein translocation

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