ref(2)P

1. ref(2)P increases trauma sensitivity in flies (Ref(2)P mutants (Ref(2)Pc/e, Ref(2)Pe/+)).

   “autophagy mutants (Atg8a1, Ref(2)Pc/e, Ref(2)Pe/+) showed heightened trauma sensitivity”

   Model organismsRef(2)P mutants (Ref(2)Pc/e, Ref(2)Pe/+)

   Genetic Modifiers Influencing the Acute and Long-Term Responses to Traumatic Brain Injury in Drosophila

   bioRxiv (Cold Spring Harbor Laboratory)·Feb 15, 2025Preprint

1. ref(2)P decreases mitochondrial superoxide in flies (ref(2)P point mutation disrupting Atg8a binding).

   “reduced levels of aging-associated mitochondrial superoxide”

   Model organismsref(2)P point mutation disrupting Atg8a binding

   Loss of ubiquitinated protein autophagy is compensated by persistent cnc/NFE2L2/Nrf2 antioxidant responses

   Autophagy·Feb 20, 2022

More on Mitochondrial superoxide

1. ref(2)P activates NRF2–KEAP1 antioxidant response in flies (ref(2)P point mutation disrupting Atg8a binding).

   “results in the co-sequestering of Keap1 and thus activates the cnc/NFE2L2/Nrf2 antioxidant pathway”

   Model organismsref(2)P point mutation disrupting Atg8a binding

   Loss of ubiquitinated protein autophagy is compensated by persistent cnc/NFE2L2/Nrf2 antioxidant responses

   Autophagy·Feb 20, 2022

More on NRF2–KEAP1 antioxidant response

1. ref(2)P showed no clear effect on healthspan in flies (ref(2)P point mutation disrupting binding to Atg8a).

   “has hardly any effect on bulk autophagy, proteasome activity and fly healthspan”

   Model organismsref(2)P point mutation disrupting binding to Atg8a

   Loss of ubiquitinated protein autophagy is compensated by persistent cnc/NFE2L2/Nrf2 antioxidant responses

   Autophagy·Feb 20, 2022

1. ref(2)P increases intestinal regeneration in flies (without autophagy-mediated suppression; via yki activation).

   “accumulation of a receptor protein of selective autophagy, ref(2)P, continuously acts as a signaling platform to cause excessive regeneration via cytokine production by yki (yorkie) activation”

   Reviewwithout autophagy-mediated suppression; via yki activationintestine

   Selective autophagy tolerates symbiotic bacteria in the Drosophila intestine

   Autophagy·Mar 19, 2021

1. ref(2)P improves mitochondrial function in flies (midlife induction).

   “upregulating dp62, in midlife, promotes mitochondrial fission, facilitates mitophagy, and improves mitochondrial function in aged flies”

   Model organismsmidlife induction

   Upregulation of the Autophagy Adaptor p62/SQSTM1 Prolongs Health and Lifespan in Middle-Aged Drosophila

   Cell reports·Jul 23, 2019

1. ref(2)P activates mitophagy in flies (midlife induction).

   “upregulating dp62, in midlife, promotes mitochondrial fission, facilitates mitophagy, and improves mitochondrial function in aged flies”

   Model organismsmidlife induction

   Upregulation of the Autophagy Adaptor p62/SQSTM1 Prolongs Health and Lifespan in Middle-Aged Drosophila

   Cell reports·Jul 23, 2019

More on Mitophagy

1. ref(2)P improves proteostasis in flies (autophagy-dependent; midlife induction).

   “Midlife induction of dp62 improves proteostasis, in aged flies, in an autophagy-dependent manner”

   Model organismsautophagy-dependent; midlife induction

   Upregulation of the Autophagy Adaptor p62/SQSTM1 Prolongs Health and Lifespan in Middle-Aged Drosophila

   Cell reports·Jul 23, 2019

More on Proteostasis

1. ref(2)P extends lifespan in flies (midlife induction).

   “upregulating the Drosophila p62 homolog ref(2)P/dp62, starting in midlife, delays the onset of pathology and prolongs healthy lifespan”

   Model organismsmidlife induction

   Upregulation of the Autophagy Adaptor p62/SQSTM1 Prolongs Health and Lifespan in Middle-Aged Drosophila

   Cell reports·Jul 23, 2019