A historical perspective of macroautophagy regulation by biochemical and biomechanical stimuli
Autophagy is stimulated by starvation (amino acids and/or glucose deprivation) and growth factor limitation. In addition, mechanical forces are also positive regulators of autophagy. Growth factors and mechanical forces trigger signaling from the cell surface including from the primary cilium (PC) whereas nutrients directly act intracellularly. Many of the stimuli that control autophagy converge on the kinases mTOR and AMPK. Macroautophagy is a lysosomal degradative pathway for intracellular macromolecules, protein aggregates and organelles. The formation of the autophagosome, a double membrane-bound structure that sequest...
Source: FEBS Letters - October 1, 2023 Category: Biochemistry Authors: Nicolas Dupont, Aurore Claude ‐Taupin, Patrice Codogno Tags: Review Source Type: research

Design and engineering of artificial biosynthetic pathways – where do we stand and where do we go?
Microbial production of commodity and specialty chemicals has the potential to decrease our reliance on fossil fuels and reduce the accompanying environmental effects. The scope of traditional biomanufacturing can be greatly enhanced by constructing new-to-nature pathways towards target chemicals. Here, we outline the principles of artificial pathway design and engineering, highlight notable examples and provide an outlook on its future. The production of commodity and specialty chemicals relies heavily on fossil fuels. The negative impact of this dependency on our environment and climate has spurred a rising demand for mo...
Source: FEBS Letters - October 1, 2023 Category: Biochemistry Authors: Nika Sokolova, Bo Peng, Kristina Haslinger Tags: Review Source Type: research

The magnified view: from ancient trinkets to single nuclear pore complexes
A journey from the polished quartz lenses in the eyes of an ancient Egyptian statue of a seated scribe, through the development of microscopes and towards modern electron microscopy. Recent advances in field emission scanning electron microscopy have made it possible to expose nuclei from human cells and to focus on individual nuclear pore complexes, comparing their architectural features. A journey from the earliest known use of lenses and magnifying glasses in ancient times, through the development of microscopes and towards modern electron microscopy techniques. The evolving technology and improved microscopes enabled t...
Source: FEBS Letters - October 1, 2023 Category: Biochemistry Authors: Boris Fichtman, Amnon Harel Tags: In a Nutshell Source Type: research

Structural dynamics at the active site of the cancer ‐associated flavoenzyme NQO1 probed by chemical modification with PMSF
We report the crystal structure of NQO1 with phenylmethylsulfonyl fluoride (PMSF) covalently bound to the Tyr128 residue. We show that, unexpectedly, the catalytic activity of the enzyme was not abolished, indicating that the PMSF molecule does not limit the dynamics of this residue. A large conformational heterogeneity of human NAD(P)H:quinone oxidoreductase 1 (NQO1), a flavoprotein associated with various human diseases, has been observed to occur in the catalytic site of the enzyme. Here, we report the X-ray structure of NQO1 with phenylmethylsulfonyl fluoride (PMSF) at 1.6  Å resolution. Activity assays confirmed th...
Source: FEBS Letters - September 30, 2023 Category: Biochemistry Authors: Alice Grieco, Miguel A. Ruiz ‐Fresneda, Atanasio Gómez‐Mulas, Juan Luis Pacheco‐García, Isabel Quereda‐Moraleda, Angel L. Pey, Jose M. Martin‐Garcia Tags: Research Letter Source Type: research

The magnified view: from ancient trinkets to single nuclear pore complexes
A journey from the polished quartz lenses in the eyes of an ancient Egyptian statue of a seated scribe, through the development of microscopes and towards modern electron microscopy. Recent advances in field emission scanning electron microscopy have made it possible to expose nuclei from human cells and to focus on individual nuclear pore complexes, comparing their architectural features. A journey from the earliest known use of lenses and magnifying glasses in ancient times, through the development of microscopes and towards modern electron microscopy techniques. The evolving technology and improved microscopes enabled t...
Source: FEBS Letters - September 30, 2023 Category: Biochemistry Authors: Boris Fichtman, Amnon Harel Tags: In a Nutshell Source Type: research