Protein homeostasis is the core response of cells against stress. As an important organelle, mitochondria depend on a complex network of protein to perform normal functions, therefore protein homeostasis is significant to mitochondria. When the organism is exposed to external pressure, it produces alterations in protein homeostasis. In order to maintain the normal function, cells activate a transcriptional response mechanism called mitochondrial unfolded protein response (UPR^mt), which maintains mitochondrial protein homeostasis and restores mitochondrial function to cope with stress and maintain organism health. In this review, we present an overview of the relationship between mitochondrial protein homeostasis and UPR^mt, and focus on summarizing the relevant mechanisms associated with cell-autonomous and non-autonomous UPR^mt in C. elegans. Among them, the cell- autonomous UPR^mt contains the basic signaling pathways involved in transcription factors ATFS-1, DVE-1, UBL-5 and epigenetic mechanisms related to acetylation and methylation in histone modifications. In addition, although the downstream molecular mechanism is not clear, a novel signaling pathway, SPHK-1/S1P, independent of these common transcription factors, can also activate UPR^mt. Recently, in analogy to “cytokines”, a variety of factors produced by mitochondrial stress as “mitokines” has been found that participate in UPR^mt activation among different tissues. The neurotransmitter 5-HT, neuropeptide FLP-2, intercellular secretory factor WNT/egl-20, and FSHR-1 are involved in the neuronal-intestinal UPR^mt. Despite that the factor between germline and intestine is not found, mitochondrial CYC-2.1 reducing in germline still activates UPR^mt of intestinal cells. This is probably a self-protection and repair mechanism in evolution, which acts as “early warning” and activates the repair effect of distal tissues to respond rapidly and efficiently to the challenges posed by external damage. We also discuss the impact of UPR^mt on ageing. Affecting the imbalance between nDNA and mtDNA-encoded proteins in mitochondria can effectively induce UPR^mt and extend lifespan. In terms of stress responses, UPR^mt is beneficial to maintaining protein homeostasis by activating transcription and translation, causing metabolic reorganization, however, the activation of UPR^mt is not a sufficient condition for longevity. Perhaps the life-extending effect is just an additional benefit of UPR^mt on stress relief, or mild, short-term, qualified UPR^mt can extend lifespan, while strong, long-term, generalized UPR^mt activation may irrelevant. It provides new theoretical basis for further research.