Custom instructions barely work

Does anyone else find custom-instructions barely work?

For example, my custom instruction is just not to use lists, and 90% of the time my answers have lists.

For example here is a custom instruction, question, and answer that completely disregards the instructions:

Custom instruction:
"Answer in paragraphs by default. Do not use lists in your answer unless I ask. Never use nested-lists in your response.

Remember:
Do not use lists in your answer unless I ask for lists
Do not use bulleted-lists in your answer unless I ask for lists
Always answer with paragraphs unless I ask for lists"

Question:
Is the endosome an autophagosome? What is the differences and similarities between endosome and autophagosome?

Answer:
No, the endosome is not an autophagosome; they are separate and distinct structures within the cell, each with its unique functions and characteristics. Here’s an exploration of their differences and similarities:

Differences:

  1. Function: Endosomes are involved in the sorting, recycling, and degradation of materials taken up from outside the cell through endocytosis. Autophagosomes, on the other hand, are part of the autophagy pathway, responsible for encapsulating and degrading damaged or unnecessary intracellular components.
  2. Structure: Endosomes are single-membrane vesicles, while autophagosomes are characterized by a unique double-membrane structure.
  3. Formation and Molecular Machinery: The formation of endosomes and autophagosomes involves different sets of proteins and molecular machinery. Endosomes form through the invagination of the plasma membrane, while autophagosomes form around the cellular materials targeted for degradation.
  4. Pathway Involvement: Endosomes are part of the endocytic pathway, whereas autophagosomes are central to the autophagy pathway.

Similarities:

  1. Membrane-Bound Compartments: Both endosomes and autophagosomes are membrane-bound vesicles within the cell.
  2. Involvement in Degradation: Both structures are involved in degradation processes. Endosomes can eventually fuse with lysosomes to degrade their contents, similar to how autophagosomes fuse with lysosomes to form autolysosomes for degradation.
  3. Interaction with Lysosomes: Both endosomes and autophagosomes can fuse with lysosomes. In the case of endosomes, this leads to the degradation of internalized materials. For autophagosomes, this fusion results in the degradation of enclosed damaged or unnecessary cellular components.
  4. Role in Cellular Homeostasis: Both endosomes and autophagosomes play vital roles in maintaining cellular homeostasis by regulating the recycling and degradation of cellular materials.

In summary, while endosomes and autophagosomes share some similarities in their membrane-bound nature and involvement in degradation processes, they are fundamentally different in their functions, structures, and the pathways they are part of. These differences reflect their specialized roles in handling different aspects of cellular material processing and recycling.