Mitochondrial protein import stress regulates the LC3 lipidation step of mitophagy through NLRX1 and RRBP1

Killackey, Samuel A.; Bi, Yuntian; Soares, Fraser; Hammi, Ikram; Winsor, Nathaniel J; Abdul-Sater, Ali A.; Philpott, Dana J.; Arnoult, Damien; Girardin, Stephen E.

doi:10.1016/j.molcel.2022.06.004

Cited by 32 publications

(33 citation statements)

References 56 publications

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“…The ER wraps around mitochondria to modulate lipid flux requiring ER-resident Rrbp1 for ER-mitochondria interactions, specifically at MAMs (mitochondrial-associated ER membranes) such that silencing of Rrbp1 in liver gave rise to steatosis ( 71 ). Rrbp1 also stimulates mitophagy in skeletal muscle by promoting LC3 lipidation ( 72 ), suggesting a broader role for Rrbp1 in lipid homeostasis through interactions at the mitochondria and the ER. While we have not detected BNIP3 at other subcellular locations other than mitochondria, future work will examine whether BNIP3 is enriched at sites of mitochondrial contact with ER (MAMs) and mitochondrial-LD contacts.…”

Section: Discussionmentioning

confidence: 99%

Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner

et al. 2022

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Hepatic steatosis is a major etiological factor in hepatocellular carcinoma (HCC), but factors causing lipid accumulation leading to HCC are not understood. We identify BNIP3 (a mitochondrial cargo receptor) as an HCC suppressor that mitigates against lipid accumulation to attenuate tumor cell growth. Targeted deletion of Bnip3 decreased tumor latency and increased tumor burden in a mouse model of HCC. This was associated with increased lipid in bnip3 −/− HCC at early stages of disease, while lipid did not accumulate until later in tumorigenesis in wild-type mice, as Bnip3 expression was attenuated. Low BNIP3 expression in human HCC similarly correlated with increased lipid content and worse prognosis than HCC expressing high BNIP3. BNIP3 suppressed HCC cell growth by promoting lipid droplet turnover at the lysosome in a manner dependent on BNIP3 binding LC3. We have termed this process “mitolipophagy” because it involves the coordinated autophagic degradation of lipid droplets with mitochondria.

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Section: Discussionmentioning

confidence: 99%

Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner

et al. 2022

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“…A homeostatic shift towards mitophagy (the selective autophagic elimination of damaged mitochondria by the lysosome) is initiated when the capacity of nanoscale proteostasis or MDVs is exceeded [95,96].…”

Section: Trends In Neurosciencesmentioning

confidence: 99%

Mitochondrial signalling and homeostasis: from cell biology to neurological disease

Collier¹,

Oláhová²,

McWilliams³

et al. 2023

Trends in Neurosciences

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“…It was observed in yeast that mitochondrial protein import stress triggers mitophagy to eliminate mitochondria that undergo dysfunctional protein import ( Killackey et al., 2022 ). The U-box 4 (PUB4) E3 ubiquitin ligase was demonstrated to mediate the clearance of 1 O 2 -damaged chloroplasts by chlorophagy ( Woodson et al., 2015 ).…”

Section: Chloroplast Protein Import Stress and Its Interaction With T...mentioning

confidence: 99%

Chloroplast proteostasis: A story of birth, life, and death

Gao¹,

Hong²,

Wang³

et al. 2023

Plant Communications

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Mitochondrial protein import stress regulates the LC3 lipidation step of mitophagy through NLRX1 and RRBP1

Cited by 32 publications

References 56 publications

Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner

Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner

Mitochondrial signalling and homeostasis: from cell biology to neurological disease

Chloroplast proteostasis: A story of birth, life, and death

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