Figure 1. Effect of lithium chloride and pEGFP-N1-BmK CT on C6 glioma cells proliferation. (Fu Y, et al., 2016)
FAM162A regulates OPA1 expression levels
FAM162A Is a Key Regulator of Mitochondrial Structure, Dynamics, and Bioenergetics, Driving Cellular Protection and Longevity
Paper
2026
Aging Cell |
DOI
Background
FAM162A, an inner mitochondrial protein previously linked to hypoxia-induced apoptosis, is shown here to play a broader protective role. The study reveals that FAM162A localizes predominantly within mitochondrial cristae, where it supports cristae ultrastructure, mitochondrial dynamics, bioenergetics, and turnover. Mechanistically, FAM162A interacts with OPA1 and modulates the balance between long and short OPA1 isoforms. Loss of FAM162A impairs respiration, membrane potential, mitochondrial morphology, and cell survival, while overexpression enhances oxidative metabolism, stress resistance, mitochondrial turnover, and longevity in transgenic Drosophila, identifying FAM162A as a key gatekeeper of mitochondrial integrity and cellular health.
Key Findings
This study establishes FAM162A as a conserved inner mitochondrial membrane protein localized mainly in cristae, with both termini facing the matrix. Loss-of-function experiments in COS7 cells showed that FAM162A silencing reduces cell viability, increases apoptosis and cytochrome c release, decreases mitochondrial membrane potential and oxygen consumption, and disrupts mitochondrial network morphology and cristae ultrastructure. FAM162A was found to interact with OPA1 and positively regulate OPA1 protein levels, shifting the balance from long to short OPA1 isoforms when silenced. Gain-of-function experiments demonstrated that FAM162A overexpression enhances basal, maximal, and spare respiratory capacity, promotes mitochondrial ATP production, and shifts metabolism toward oxidative phosphorylation. It also reduces mitochondrial oxidation under paraquat-induced stress, indicating improved mitochondrial turnover. Transgenic Drosophila overexpressing human FAM162A exhibited significantly extended lifespan, especially in females, and improved survival and locomotor activity under heat stress. Overall, FAM162A emerges as a mitochondrial cristae regulator that sustains bioenergetics, stress resistance, and longevity through mechanisms involving OPA1.
Contribution
Creative Biogene contributed by supplying the pEGFP-N1 (OVT2585) plasmid used as a control and transfection tool in fluorescence protease protection and live-cell imaging experiments, enabling the validation of FAM162A localization, topology, and mitochondrial functional analyses.
FAM162A, an inner mitochondrial protein previously linked to hypoxia-induced apoptosis, is shown here to play a broader protective role. The study reveals that FAM162A localizes predominantly within mitochondrial cristae, where it supports cristae ultrastructure, mitochondrial dynamics, bioenergetics, and turnover. Mechanistically, FAM162A interacts with OPA1 and modulates the balance between long and short OPA1 isoforms. Loss of FAM162A impairs respiration, membrane potential, mitochondrial morphology, and cell survival, while overexpression enhances oxidative metabolism, stress resistance, mitochondrial turnover, and longevity in transgenic Drosophila, identifying FAM162A as a key gatekeeper of mitochondrial integrity and cellular health.
Key Findings
This study establishes FAM162A as a conserved inner mitochondrial membrane protein localized mainly in cristae, with both termini facing the matrix. Loss-of-function experiments in COS7 cells showed that FAM162A silencing reduces cell viability, increases apoptosis and cytochrome c release, decreases mitochondrial membrane potential and oxygen consumption, and disrupts mitochondrial network morphology and cristae ultrastructure. FAM162A was found to interact with OPA1 and positively regulate OPA1 protein levels, shifting the balance from long to short OPA1 isoforms when silenced. Gain-of-function experiments demonstrated that FAM162A overexpression enhances basal, maximal, and spare respiratory capacity, promotes mitochondrial ATP production, and shifts metabolism toward oxidative phosphorylation. It also reduces mitochondrial oxidation under paraquat-induced stress, indicating improved mitochondrial turnover. Transgenic Drosophila overexpressing human FAM162A exhibited significantly extended lifespan, especially in females, and improved survival and locomotor activity under heat stress. Overall, FAM162A emerges as a mitochondrial cristae regulator that sustains bioenergetics, stress resistance, and longevity through mechanisms involving OPA1.
Contribution
Creative Biogene contributed by supplying the pEGFP-N1 (OVT2585) plasmid used as a control and transfection tool in fluorescence protease protection and live-cell imaging experiments, enabling the validation of FAM162A localization, topology, and mitochondrial functional analyses.