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Review
. 2022 May 20;11(10):1703.
doi: 10.3390/cells11101703.

Unveiling the Function of the Mitochondrial Filament-Forming Protein LACTB in Lipid Metabolism and Cancer

Annunziata Cascone  1 , Maciej Lalowski  2 , Dan Lindholm  1   3 , Ove Eriksson  1
Affiliations
Review

Unveiling the Function of the Mitochondrial Filament-Forming Protein LACTB in Lipid Metabolism and Cancer

Annunziata Cascone et al. Cells. .

Abstract

LACTB is a relatively unknown mitochondrial protein structurally related to the bacterial penicillin-binding and beta-lactamase superfamily of serine proteases. LACTB has recently gained an increased interest due to its potential role in lipid metabolism and tumorigenesis. To date, around ninety studies pertaining to LACTB have been published, but the exact biochemical and cell biological function of LACTB still remain elusive. In this review, we summarise the current knowledge about LACTB with particular attention to the implications of the recently published study on the cryo-electron microscopy structure of the filamentous form of LACTB. From this and other studies, several specific properties of LACTB emerge, suggesting that the protein has distinct functions in different physiological settings. Resolving these issues by further research may ultimately lead to a unified model of LACTB's function in cell and organismal physiology. LACTB is the only member of its protein family in higher animals and LACTB may, therefore, be of particular interest for future drug targeting initiatives.

Keywords: LACTB; cancer; lipid metabolism; mitochondria; serine protease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structural elements of LACTB: MTS, mitochondrial targeting signal; PBP-βL, penicillin-binding and beta-lactamase homology domain; MR, middle region. The location of the potential IAP-protein binding N-terminal peptide motif in LACTB is indicated. Below a sequence comparison of IAP-protein binding motifs in the mitochondrial intermembrane space proteins SMAC and HtrA2.
Figure 2
Figure 2
Comparison of the beta-lactamase fold of LACTB with that of the bacterial PBP-βLs protein flp. Panel (A): LACTB (P83111); panel (B): flp protein of Staphylococcus aureus (Q7A5Q5). The locations of the catalytic site residues in the signature motifs [3] are marked in red, -SISK-, -YST-, and -HTG- for LACTB, and -SNTK-, -YSN-, and -HSG- for the fpl protein. The structure of LACTB was determined by cryo-electron microscopy [2] and that of flp by X-ray crystallography [42]. The image was generated partially using SWISS-MODEL [43].
See this image and copyright information in PMC

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