Review Mitochondrial quality control pathways sense mitochondrial protein import, 2023, Laurie P. Lee-Glover and Timothy E. Shutt

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Mitochondrial quality control pathways sense mitochondrial protein import
Laurie P. Lee-Glover; Timothy E. Shutt

Mitochondrial quality control (MQC) mechanisms are required to maintain a functional proteome, which enables mitochondria to perform a myriad of important cellular functions from oxidative phosphorylation to numerous other metabolic pathways. Mitochondrial protein homeostasis begins with the import of over 1000 nuclear-encoded mitochondrial proteins and the synthesis of 13 mitochondrial DNA-encoded proteins. A network of chaperones and proteases helps to fold new proteins and degrade unnecessary, damaged, or misfolded proteins, whereas more extensive damage can be removed by mitochondrial-derived vesicles (MDVs) or mitochondrial autophagy (mitophagy).

Here, focusing on mechanisms in mammalian cells, we review the importance of mitochondrial protein import as a sentinel of mitochondrial function that activates multiple MQC mechanisms when impaired.


Link | Paywall (Trends in Endocrinology & Metabolism)

 

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Review article, concluding —

Our view of mitochondria as static energy producers has long been transformed to encompass a dynamic role as a metabolic signaling hub. Beyond signaling to other organelles, mitochondria can communicate with the organism as a whole. Mitochondrial stress in one cell or tissue can generate a ‘mitokine’ signal that activates a stress response in other locations. [...] In mammalian tissues, mitochondrial stress in skeletal muscles induces compensation in adipose by the release of FGF21.

One area of future research may be steroid hormones, signaling molecules that function as long-range messengers throughout the body and also influence mitochondrial function such as ΔΨm [mitochondrial membrane potential]. Intriguingly, as described earlier, the steroid metabolism protein HSD17B10 is also a mitochondrial stress response protein. Another interesting MQC candidate is the protein STARD1, which mediates mitochondrial import of cholesterol, the rate-limiting step of steroid production. STARD1 promotes mitochondrial cholesterol import when it is transiently associated with the OMM, prior to its import into the matrix, and slowing mitochondrial protein import increases cholesterol import. Thus, impairments in mitochondrial protein import homeostasis may alter steroid signaling through synthesis or metabolism, with the potential to translate mitochondrial defects to organism-wide signaling.