Mitochondrial protein import machinery conveys stress signals to the cytosol and beyond

Mitochondria hold diverse and pivotal roles in fundamental processes that govern cell survival, differentiation, and death, in addition to organismal growth, maintenance, and aging. The mitochondrial protein import system is a major contributor to mitochondrial biogenesis and lies at the crossroads between mitochondrial and cellular homeostasis. Recent findings highlight the mitochondrial protein import system as a signaling hub, receiving inputs from other cellular compartments and adjusting its function accordingly. Impairment of protein import, in a physiological, or disease context, elicits adaptive responses inside and outside mitochondria. In this review, we discuss recent developments, relevant to the mechanisms of mitochondrial protein import regulation, with a particular focus on quality control, proteostatic and metabolic cellular responses, triggered upon impairment of mitochondrial protein import.

Automated summary

Mitochondria play diverse and crucial roles in fundamental cellular processes and organismal function, and the protein import system is a key component linking mitochondrial and cellular homeostasis. Recent research indicates that the mitochondrial protein import system acts as a signaling hub, receiving inputs from other cellular compartments and adjusting its function accordingly. Impairment of protein import elicits adaptive responses both inside and outside mitochondria, and this review discusses the mechanisms of mitochondrial protein import regulation, with a focus on quality control, proteostatic and metabolic cellular responses triggered by its impairment.