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Mitochondria contain multisubunit translocases to import preproteins from the cytosol. The presequence translocase of the inner membrane operates in a voltage-gated manner, but how a preprotein-conducting channel responds to the membrane potential was unknown. A new study identifies a voltage-coupled conformational change in a transmembrane segment of the Tim23 import channel, representing a major step toward understanding the molecular basis of a voltage-gated protein translocase.

The sorting and assembly machinery (SAM) mediates mitochondrial β-barrel protein folding and membrane insertion. A cryo-EM structure of the yeast SAM complex bound to an early eukaryotic β-barrel intermediate reveals a multipoint guidance mechanism.

An analysis of MitCOM—a comprehensive resource for the identification, organization and interaction of mitochondrial machineries and pathways in yeast—identifies a constitutive pathway for the removal of preproteins.

Proteins are inserted into the outer mitochondrial membrane by the mitochondrial sorting and assembly machinery, two structural forms of which are presented here, suggesting the mechanism involved.

Many proteins destined for the inner mitochondrial membrane are imported via amino-terminal targeting sequences that are subsequently cleaved. Ieva et al.identify an alternative mechanism for mitochondrial protein import that depends on a carboxyl-terminal targeting sequence.

The protein Mdm10 is known to be present in the endoplasmic reticulum-mitochondria encounter structure (ERMES) and in mitochondrial sorting and assembly machinery (SAM). Here, the authors examine how this protein interacts with SAM and EMRES, showing that the SAM-mediated protein machinery is independent of ERMES.

Proteomic studies have led to the identification of numerous new transport components and pathways for mitochondrial protein import. Furthermore, they have revealed that protein translocases are integrated into dynamic networks and are connected to machineries that function in bioenergetics, mitochondrial morphology and coupling to the endoplasmic reticulum.

Prostate cancer growth depends on de novo lipogenesis controlled by the mitochondrial pyruvate dehydrogenase complex (PDC). Here the authors find that a histone methyltransferase KMT9 is localized in the mitochondria of prostate cancer cells to regulate PDC activity by methylating its subunit DLAT.

Proteins imported into mitochondria must be unfolded in order to pass through translocation pores present in the mitochondrial membranes. An article in this issue suggests that not only the heat shock protein 70 in the matrix, but also the electrical membrane potential across the inner membrane can actively unfold preproteins via a pulling mechanism.

The high-resolution cryo-electron microscopy structure of the yeast translocase of the outer mitochondrial membrane reveals key features of mitochondrial protein import that are conserved in all eukaryotes.

Guhathakurta et al. describe the acetyltransferase activity of MOF in the mitochondria. MOF can acetylate COX17, thus contributing to the assembly and function of respiratory complex IV. These findings provide better understanding of how mitochondrial function is fine-tuned by acetylation.

Cells respond to mitochondrial protein import stress by regenerating clogged import sites and inducing stress responses. Mitochondria are thus tightly integrated into the cellular proteostasis and stress-response network to maintain cell viability.

Few tools are available to identify active membrane proteins within their native lipid environment. Here, Gold et al. report on a strategy that can be used for site-specific labelling of membrane proteins via electron cryotomography.

The MICOS complex has an essential role in crista junction formation and mitochondrial inner membrane morphology. Here, the authors show that one of its components, Mic60, known to form contact sites between inner and outer membranes, also displays membrane-shaping activity.

Recent functional and proteomic studies have revealed the remarkable complexity of mitochondrial protein organization and interactions. This Review discusses how the mitochondrial protein import machinery functions as a key organizer of these protein networks, its involvement in the formation of membrane contact sites, and how defects in protein import can lead to disease.

Mitochondria and chloroplasts import the vast majority of their proteins across two membranes. Although the import and initial sorting of precursor proteins is mediated by translocases that are functionally similiar in the outer membrane of both organelles, they each have a unique mode of translocation.

Respiratory chain subunits are made up of proteins encoded by nuclear and mitochondrial DNA, which assemble to form functional enzymes. New findings reveal that the mitochondrial translation of Cox1, the core component of cytochromecoxidase, is directly coupled to the assembly of this respiratory complex.